Skip to main content
SpringerLink
Log in

Mechanisms of tumor invasion: evidence from in vivo observations

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Summary

The major mechanisms of tumor invasion in vivo are discussed in the present review. A special emphasis is placed on tumor dedifferentiation which has proved to be of paramount importance for the invasion process. Based on in vivo observations obtained from various human and animal tumors a concept for the mechanism of tumor invasion is proposed which mainly comprises the following basic events: the first and essential step in tumor invasion is the tumor dedifferentiation and dissociation at the invasion front. This apparently temporary and reversible process mobilizes the tumor cells out of the main tumor bulk and enables them to invade the host tissue by active locomotion. This mechanism is essentially supported by an interstitial edema in the host tissue adjacent to the tumor periphery, which causes an ‘opening and widening’ of the host intercellular spaces. Enzymatic changes in the micromilieu of the extracellular matrix may contribute to this process. The tumor cell proliferation completes the invasion process in so far, as the invading tumor cells are still able to proliferate, leading this way to expanding tumor cell nests in the host tissue which have the potency to redifferentiate. The expansive growth of these tumor cell nests results in a progressive atrophy of the host tissue, mainly caused by an increasing compression and a competitive withdrawal of oxygen and other nutrients by the tumor cells. The overall picture of tumor invasion can therefore be considered as a repetitive cycle of active tumor cell locomotion followed by focal tumor cell proliferation in the host tissue.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Albrechtsen, R, Nielsen, M, Wewer, U, Engvall, E, Kuoslahti, E: Basement membrane changes in breast cancer detected by immuno-histochemical staining for laminin. Cancer Res 41: 5076–5081, 1981

    Google Scholar 

  2. Alroy, J, Pauli, BU, Weinstein, RS: Correlation between numbers of desmosomes and the aggressiveness of transitional cell carcinoma in human urinary bladder. Cancer 47: 104–112, 1981

    Google Scholar 

  3. Ambrose, EJ, Easty, DM: Time-lapse filming of cellular interactions within living tissues. III. The role of cell shape. Differentiation 6: 61–70, 1976

    Google Scholar 

  4. Ashworth, CT, Stembridge, VA, Luibel, FJ: A study of basement membranes of normal epithelium, carcinoma in situ and invasive carcinoma of uterine cervix utilizing electron microscopy and histochemical methods. Acta cytol 5: 369–384, 1961

    Google Scholar 

  5. Babai, F: Etude ultrastructurale sur la pathogénie de l'invasion du muscle strié par des tumeurs transplantables. J Ultrastruct Res 56: 287–303, 1976

    Google Scholar 

  6. Barnett, SC, Eccles, SA: Studies of mammary carcinoma metastasis in a mouse model system. I: Derivation and characterization of cells with different metastatic properties during tumour progression in vivo. Clin Expl Metastasis 2: 15–36, 1984

    Google Scholar 

  7. Bannasch, P, Zerban, H, Mayer, D: The cytoskeleton in tumor cells. Path Res Pract 175: 196–211, 1982

    Google Scholar 

  8. Beesley, JE, Pearson, JD, Hutchings, A, Carleton, JS, Gordon, JL: Granulocyte migration through endothelium in culture. J Cell Sci 38: 237–248, 1979

    Google Scholar 

  9. Belnap, LP, Cleveland, PH, Colmerauer, MEM, Barone, RM, Pilch, YH: Immunogenicity of chemically induced murine colon cancers. Cancer Res 39: 1174–1179, 1979

    Google Scholar 

  10. Berenblum, I: The nature of tumour growth. In: Florey, HW (ed): General pathology. Loyd-Luke, London, 1970, pp 645–667

    Google Scholar 

  11. Biswas, C: Host-tumor cell interactions and collagenase activity. In: Liotta, LA, Hart, I (eds) Tumor invasion and metastasis. Martinus Nijhoff Publishers, The Hague, Boston, London, 1982, pp 405–425

    Google Scholar 

  12. Bonk, U, Coutelle, C, Felicetti, D, Rath, FW, Traub, F: Vergleichende histologische und elektronenmikroskopische sowie histo-und biochemische Untersuchungen zum invasiven Tumorwachstum. II. Elektronenmikroskopische Untersuchung. Exp Path 4: 16–32, 1970

    Google Scholar 

  13. Brawn, PN: The dedifferentiation of prostate carcinoma. Cancer 52: 246–251, 1983

    Google Scholar 

  14. Broyn, T: Cell proliferation in Walker tumour growing in the stomach wall. Cell Tissue Kinet 8: 413–422, 1975

    Google Scholar 

  15. Burgess, EA, Sylven, B: Glucose, lactate, and lactic dehydrogenase activity in normal interstitial fluid and that of solid mouse tumors. Cancer Res 22: 581–588, 1962

    Google Scholar 

  16. Busch, H: An introduction to the biochemistry of the cancer cell. H., Busch (ed) Academic Press, New York, London, 1962

    Google Scholar 

  17. Butler, TP, Grantham, FH, Gullino, PM: Bulk transfer of fluid in the interstitial compartment of mammary tumors. Cancer Res 35: 3084–3088, 1975

    Google Scholar 

  18. Camplejohn, RS, Bone, G, Aherne, W: Cell proliferation in rectal carcinoma and rectal mucosa. A stathmokinetic study. Europ J Cancer 9: 577–581, 1973

    Google Scholar 

  19. Carr, I, Norris, P, McGinty, F: Reverse diapedesis; the mechanism of invasion of lymphatic vessels by neoplastic cells. Experientia (Basel) 31: 590–591, 1975

    Google Scholar 

  20. Carr, I, McGinty, F, Norris, P: The fine structure of neoplastic invasion: Invasion of liver, skeletal muscle and lymphatic vessel by Rd/3 tumour. J Path 118: 91–99, 1976

    Google Scholar 

  21. Casley-Smith, JR: The functioning and interrelationship of blood capillaries and lymphatics. Experientia 32: 1–12, 1976

    Google Scholar 

  22. Coutelle, C, Bonk, U, Coutelle, R, Felicetti, D, Rath, FW, Traub, F: Vergleichende histologische und elektronenmikroskopische sowie histo- und biochemische Untersuchungen zum invasiven Tumorwachstum. I. Histologische Untersuchungen. Arch Geschwulstforsch 34: 13–24, 1969

    Google Scholar 

  23. David, H, Mangakis, N: Zur Frage des invasiv-infiltrativen Wachstums von Krebszellen. Arch Geschwulstforsch 22: 92–105, 1963

    Google Scholar 

  24. De, Bruyn, PPH, Cho, Y: Vascular endothelial invasion via transcellular passage by malignant cells in the primary stage of metastases formation. J Ultrastruct Res 81: 189–201, 1982

    Google Scholar 

  25. Dingemans, KP: Behaviour of intravenously injected malignant lymphoma cells. A morphologic study. J Nat Cancer Inst 51: 1883–1895, 1973

    Google Scholar 

  26. Dingemans, KP: Invasion of liver tissue by blood-borne mammary carcinoma cells. J Nat Cancer Inst 53: 1813–1824, 1974

    Google Scholar 

  27. Druckrey, H, Preussmann, R, Matzkies, F, Ivankovic, S: Selektive Erzeugung von Darmkrebs bei Ratten durch 1,2-Dimethyl-hydrazin. Naturwissenschaften 54: 285–286, 1967

    Google Scholar 

  28. Dukes, CE, Bussey, HJR: The spread of rectal cancer and its effect on prognosis. Brit J Cancer 12: 309–320, 1958

    Google Scholar 

  29. Easty, GC, Easty, DM: An organ culture system for the examination of tumor invasion. Nature 199: 1104–1105, 1963

    Google Scholar 

  30. Easty, GC: Invasion by cancer cells. In: Ambrose, EJ, Roe, FJC (eds): The biology of cancer. D. van Nostrand Company, London, Toronto, New York, Princeton, New Jersey, 1966, pp 78–90

    Google Scholar 

  31. Easty, GC, Easty, DM: In vitro systems for the study of tumour infiltration. In: Garattini, S, Franchi, G (eds): Chemotherapy of cancer dissemination and metastasis. Raven Press, New York, 1973, pp 45–50

    Google Scholar 

  32. Easty, GC, Easty, DM: In vivo and in vitro models of invasion. In: Mareel, MM, Calman, KC (eds): Invasion. Experimental and clinical implications. Oxford University Press, Oxford, New York, Tokyo, 1984, pp 24–62

    Google Scholar 

  33. Eaves, G: The invasive growth of malignant tumours as a purely mechanical process. J Path 109: 233–237, 1973

    Google Scholar 

  34. Eccles, SA: Differentiation and neoplasia. Invasion and metastasis; experimental systems. J Pathol 141: 333–353, 1983

    Google Scholar 

  35. Enneking, WF, Spanier, SS, Malawer, MM: The effect of the anatomic setting on the results of surgical procedures for soft parts sarcoma of the tigh. Cancer 47: 1005–1022, 1981

    Google Scholar 

  36. Erlandson, RA, Carstens, PHB: Ultrastructure of tubular carcinoma of the breast. Cancer 29: 987–995, 1972

    Google Scholar 

  37. Etherington, DJ, Pugh, D, Silver, IA: Collagen degradation in an experimental inflammatory lesion. Studies on the role of the macrophage. Acta biol med germ 40: 1625–1636, 1981

    Google Scholar 

  38. Fidler, IJ: Tumor heterogeneity and the biology of cancer invasion and metastasis. Cancer Res 38: 2651–2660, 1978

    Google Scholar 

  39. Fidler, IJ, Gersten, DM, Hart, IR: The biology of cancer invasion and metastasis. Advanc Cancer Res 28: 149–250, 1978

    Google Scholar 

  40. Franks, LM, Riddle, PN, Seal, P: Actin-like filaments and cell movement in human ascites tumour cells. Exp Cell Res 54: 157–162, 1969

    Google Scholar 

  41. Frei, JV: Objective measurement of basement membrane abnormalities in human neoplasms of colorectum and of breast. Histopathology 2: 107–115, 1978

    Google Scholar 

  42. Friedell, GH, Bell, JR, Burney, SW, Soto, EA, Tiltman, AJ: Histopathology and classification of urinary bladder carcinoma. Urol Clin North Am 3: 53–70, 1976

    Google Scholar 

  43. Fulker, MJ, Cooper, EH, Tanaka, T: Proliferation and ultrastructure of papillary transitional cell carcinoma of the human bladder. Cancer 27: 71–82, 1971

    Google Scholar 

  44. Gabbert, H, Höhn, P: Grades of atypia in tubular and villous adenomas of the human colon. Virchows Arch B (Cell Pathol), 33: 1–15, 1980

    Google Scholar 

  45. Gabbert, H, Wagner, R, Höhn, P: The relation between tumor cell proliferation and vascularization in differentiated and undifferentiated colon carcinomas in the rat. Virchows Arch B (Cell Pathol) 41: 119–131, 1982

    Google Scholar 

  46. Gabbert, H: Invasionsmechanismen maligner Tumoren. Verh Dtsch Ges Path 68: 18–32, 1984

    Google Scholar 

  47. Gabbert, H, Gerharz, C-D, Knuth, A, Moll, R, Sachsse, W, Wagner, R: Dimethylhydrazine-induced colonic carcinoma: characterization of a newly established rat tumor cell line in tissue culture. J Cancer Res clin Oncol 109,2: CB 17, 1985

    Google Scholar 

  48. Gabbert H, Wagner R, Moll R, Gerharz C-D: Temporary dedifferentiation, an important step in tumor invasion. Clin Expl Metastasis, in press, 1985

  49. Gabbiani, G, Csank-Brassert, J, Schneeberger, J-C, Kapanci, Y, Trenchev, P, Holborow, EJ: Contractile proteins in human cancer cells. Immunofluorescent and electron microscopic study. Am J Pathol 83: 457–474, 1976

    Google Scholar 

  50. Gabbiani, G: The cytoskeleton in cancer cells in animals and humans. Meth Achiev exp Pathol 9: 231–243, 1979

    Google Scholar 

  51. Gentili, C, Sanfilippo, O, Silvestrini, R: Cell proliferation and its relationship to clinical features and relapse in breast cancers. Cancer 48: 974–979, 1981

    Google Scholar 

  52. Gould, VE, Miller, J, Jao, W: Ultrastructure of medullary, intraductal, tubular and adenocystic breast carcinomas. Comparative patterns of myoepithelial differentiation and basal lamina deposition. Am J Pathol 78: 401–416, 1975

    Google Scholar 

  53. Gross, J, Azizkham, RG, Biswas, C, Bruns, R, Hsieh, DST, Folkman, J: Inhibition of tumor growth, vascularization, and collagenolysis in the rabbit cornea by medroxyprogesterone. Proc Natl Acad Sci USA 78: 1176–1180, 1981

    Google Scholar 

  54. Gullino, PM: Extracellular compartments of solid tumors. In: Becker, F (ed): Cancer 3. A comprehensive treatise, biology of tumors, cellular biology and growth. Plenum Press, New York, London, 1975, pp 327–354

    Google Scholar 

  55. Haemmerli, G, Sträuli, P: Motility of L 5222 leukemia cells within the mesentery. A study by time lapse cinematography. Virchows Arch B (Cell Pathol) 29: 167–177, 1978

    Google Scholar 

  56. Haemmerli, G, Arnold, B, Sträuli, P: Cell locomotion, a contributing factor in spread of the V 2 rabbit carcinoma. Int J Cancer 29: 223–227, 1982

    Google Scholar 

  57. Haemmerli, G, Arnold, B, Sträuli, P: Comparative morphology of cells located on glass and in the loose connective tissue: a study by scanning electron microscopy. Cell Biol Internat Rep 8: 689–702, 1984

    Google Scholar 

  58. Hart, R: The role of animal models in the study of experimental metastasis. In: Liotta, LA, Hart, IR (eds): Tumor invasion and metastasis. Martinus Nijhoff Publishers, The Hague, Boston, London, 1982, pp 1–14

    Google Scholar 

  59. Hartveit, F, Thoresen, S, Tangen, M, Maartmann-Moe, H: Mast cell changes and tumour dissemination in human breast carcinoma. Invasion Metastasis 4: 146–155, 1984

    Google Scholar 

  60. Hashimoto, K, Yamanishi, Y, Dabbous, MK: Electron microscopic observations of collagenolytic activity of basal cell epithelioma of the skin in vivo and in vitro. Cancer Res 32: 2561–2567, 1972

    Google Scholar 

  61. Hattori, T, Helpap, B, Gedigk, P: Development and cell kinetics of colonic tumors induced in mice by Dimethylhydrazine. J Cancer Res Clin Oncol 105: 148–157, 1983

    Google Scholar 

  62. Hayashi, H, Ishimaru, Y: Morphological and biochemical aspects of adhesiveness and dissociation of cancer cells. Int Rev Cytol 70: 139–215, 1981

    Google Scholar 

  63. Heaysman, JEM, Pegrum, SM: Early contacts between fibroblasts. An ultrastructural study. Exp Cell Res 78: 71–78, 1973

    Google Scholar 

  64. Herter, FP, Slanetz, CA: Patterns and significance of lymphatic spread from cancer of the colon and rectum. In: Weiss, L, Gilbert, HA, Ballon, SC (eds): Lymphatic system metastasis. GK Hall Medical Publishers, Boston, Massachusetts, 1982, pp 275–307

    Google Scholar 

  65. Hill, BT: The management of human ‘solid’ tumours: some observations on the irrelevance of traditional cell cycle kinetics and the value of certain recent concepts. Cell Biol Int Rep 2: 215–230, 1978

    Google Scholar 

  66. Hürter, T: Experimental brain tumors and edema in rats. II Tumor edema. Exp Path 26: 41–48, 1984

    Google Scholar 

  67. Iozzo, RV, Wight, TN: Isolation and characterization of proteoglycans synthesized by human colon carcinomas. J biol Chem 257: 11135–11144, 1982

    Google Scholar 

  68. Jokusch, BM, Haemmerli, G, In Albon, A: Cytoskeletal organization in locomoting cells of the V2 rabbit carcinoma. Exp Cell Res 144: 251–263, 1983

    Google Scholar 

  69. Jurokova, Z, Milenkov, C: Ultrastructural evidence for collagen degradation in the walls of varicose veins. Exp molec Path 37: 37–47, 1982

    Google Scholar 

  70. Kessler, DA, Langer, RS, Pless, NS, Folkman, J: Mast cells and tumor angiogenesis. Int J Cancer 18: 703–709, 1976

    Google Scholar 

  71. Lazarides, E, Weber, K: Actin antibody. The specific visualization of actin filaments in non-muscle cells. Proc Natl Acad Sci (Wash) 71: 2268–2272, 1974

    Google Scholar 

  72. Liotta, LA, Tryggvason, K, Garbisa, S, Hart, I, Foltz, CM, Shafie, S: Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature 284: 67–68, 1980

    Google Scholar 

  73. Liotta, LA: Tumor extracellular matrix. Lab Invest 47: 112–113, 1982

    Google Scholar 

  74. Lloyd, CW, Rees, DA, Smith, CG, Judge, FJ: Mechanisms of cell adhesion: early-forming junctions between aggregating fibroblasts. J Cell Sci 22: 671–684, 1976

    Google Scholar 

  75. Locker, J, Goldblatt, PJ, Leighton, J: Ultrastructure features of invasion in chick embryo liver metastasis of Yoshida ascites hepatoma. Cancer Res 30: 1632–1644, 1970

    Google Scholar 

  76. Ludatscher, RM, Luse, SA, Suntzeff, V: An electron microscopic study of pulmonary tumor emboli from transplantable Morris hepatoma 5123. Cancer Res 27: 1939–1952, 1967

    Google Scholar 

  77. MacCartney, JC, Roxburgh, J, Curran, RC: Intracellular filaments in human cancer cells: a histological study. J Path 129: 13–20, 1979

    Google Scholar 

  78. Malech, HL, Lentz, TL: Microfilaments in epidermal cancer cells. J Cell Biol 60: 473–482, 1974

    Google Scholar 

  79. Marchesi, VT, Florey, HW: Electron micrographic observations on the emigration of leucocytes. Quart J exp Physiol 45: 343–348, 1960

    Google Scholar 

  80. Mareel, MM: Recent aspects of tumor invasiveness. Int Rev Exp Pathol 22: 65–129, 1980

    Google Scholar 

  81. Mareel, MM: The use of embryo organ cultures to study invasion in vitro. In: Liotta, LA and Hart, IR (eds) Tumor invasion and metastasis. Martinus Nijhoff Publishers, The Hague, Boston, London, 1982, pp 207–230

    Google Scholar 

  82. Mareel, MM, De, Mets, M: Effect of microtubule inhibitors on invasion and on related activities of tumor cells. Int Rev Cytol 90: 125–168, 1984

    Google Scholar 

  83. Marin-Padilla, M: Erythrophagocytosis by epithelial cells of a breast carcinoma. Cancer 39: 1085–1089, 1977

    Google Scholar 

  84. McNutt, NS: Ultrastructural comparison of the interface between epithelium and stroma in basal cell carcinoma and control human skin. Lab Invest 35: 132–142, 1976

    Google Scholar 

  85. Merk, FB, Pauli, BU, Jakobs, JB, Alroy, J, Friedel, GH, Weinstein, RS: Malignant transformation of urinary bladder in humans and in N-(4-(5-nitro-2-furyl-2-thiazolyl)) formamide-exposed Fisher rats: ultrastructure of the major components of the permeability barrier. Cancer Res 37: 2843–2853, 1977

    Google Scholar 

  86. Meyvisch, C: Influence of implantation site on formation of metastases. Cancer Metast Rev 2: 295–306, 1983

    Google Scholar 

  87. Naito, Y: Studies on experimental colon tumorigenesis in rats. 2. Cell kinetics of the colon epithelium and its relation to histogenesis of colon tumors. Hiroshima J Med Sci 31: 51–61, 1982

    Google Scholar 

  88. Nicolson, GL, Birdwell, CR, Brunson, KW, Robbins, JC, Beattie, G, Fidler, IJ: Cell interactions in the metastatic process: some cell surface properties associated with succesful blood-borne tumor spread. In: Lash, JW, Burger, MM (eds) Cell and tissue interactions. Raven Press, New York, 1977, pp 225–241

    Google Scholar 

  89. Nicolson, GL, Poste, G: Tumor implantation and invasion at metastatic sites. Int Rev exptl Pathol 25: 77–181, 1983

    Google Scholar 

  90. Nicolson, GL: Cell surface molecules and tumor metastasis — Regulation of metastatic phenotypic diversity. Exp Cell Res 150: 3–22, 1984

    Google Scholar 

  91. Nigam, VN, Brailovsky, CA, Bonaventure, J: Glycosaminoglycans and proteoglycans in neoplastic tissues and their role in tumor growth and metastasis. In: Varma, RS, Varma, R, Warren, P (eds): Glycosaminoglycans and proteoglycans in physiological and pathological processes of body systems. S. Karger, Basel, 1982, pp 354–371

    Google Scholar 

  92. Ozzello, L: Electron microscopic study of functional and dysfunctional human mammary glands. J Invest Dermat 63: 19–26, 1974

    Google Scholar 

  93. Pauli, BU, Cohen, SM, Alroy, J, Weinstein, RS: Desmosome ultrastructure and the biological behaviour of chemical carcinogen-induced urinary bladder carcinomas. Cancer Res 38: 3276–3285, 1978

    Google Scholar 

  94. Pauli, BU, Schwartz, DE, Thonar, EJ-M, Kuettner, KE: Tumor invasion and host extracellular matrix. Cancer Metast Rev 2: 129–152, 1983

    Google Scholar 

  95. Peterson, HJ, Appelgren, L, Lundborg, G, Rosengren, B: Capillary permeability of two transplantable rat tumours as compared with various normal organs of the rat. Bibl anat 12: 511–518, 1973

    Google Scholar 

  96. Polak-Charcon, S, Shoham, J, Ben-Shaul, Y: Tight junctions in epithelial cells of human fetal hindgut, normal colon, and colon adenocarcinoma. J Natl Cancer Inst 65: 53–62, 1980

    Google Scholar 

  97. Pitelka, DR, Hamamoto, ST, Taggart, BN: Basal lamina and tissue recognition in malignant mammary tumors. Cancer Res 40: 1600–1611, 1980

    Google Scholar 

  98. Poste, G, Doll, J, Hart, IR, Fidler, IJ: In vitro selection of murine B 16 melanoma variants with enhanced tissue-invasive properties. Cancer Res 40: 1636–1644, 1980

    Google Scholar 

  99. Poste, G: Methods and models for studying tumor invasion. In: Liotta, LA, Hart, IR (eds): Tumor invasion and metastasis. Martinus Nijhoff Publishers, The Hague, Boston, London, 1982, pp 147–171

    Google Scholar 

  100. Pourreau-Schneider, N, Felix, H, Haemmerli, G, Sträuli, P: The role of cellular locomotion in leukemic infiltration. An organ culture study on penetration of L5222 leukemia cells into the chick embryo mesonephros. Virchows Arch B (Cell Pathol) 23: 257–264, 1977

    Google Scholar 

  101. Reinhold, HS: Improved microcirculation in irradiated tumours. Europ J Cancer 7: 273–280, 1971

    Google Scholar 

  102. Roos, E, Van de, Pavert, IV, Middlekoop, OP: Infiltration of tumour cells into cultures of isolated hepatocytes. J Cell Sci 47: 385–397, 1981

    Google Scholar 

  103. Ross, JS: Experimental large intestinal adenocarcinoma induced by hydrazines and human colorectal cancer: a comparative study. In: Malt, RA and Williamson, RCN (eds): Falk Symposion 31, Colonic carcinogenesis. MTP Press, Lancaster, Boston, The Hague, 1982, pp 187–207

    Google Scholar 

  104. Rubio, CA, Biberfeld, P: The basement membrane of the uterine cervix in dysplasia and squamous carcinoma: an immunofluorescent study with antibodies to basement membrane antigen. Acta path microbiol scand Sect A 83: 744–748, 1975

    Google Scholar 

  105. Rubio, CA: Rate of cell division in a typias and invasive carcinoma of the uterine cervix of the mouse. J Natl Cancer Inst 61: 259–263, 1978

    Google Scholar 

  106. Rungger-Brändle, E, Gabbiani, G: The role of cytoskeletal and cytocontractile elements in pathologic processes. Am J Pathol 110: 361–392, 1983

    Google Scholar 

  107. Sato, H, Suzuki, M: Experimental studies on metastasis formation with special reference to the mechanism of cancer cell lodgement in the microcirculation. Exp Med Int Congr Ser 269: 168–176, 1972

    Google Scholar 

  108. Schindler, A-M, Amaudruz, MA, Kocher, O, Riotton, G, Gabbiani, G: Desmosomes and gap-junctions in various epidermoid preneoplastic and neoplastic lesions of the cervix uteri. Acta Cytol 26: 466–470, 1982

    Google Scholar 

  109. Sherbet, GV: The biology of tumour malignancy. Sherbet, GV (ed) Academic Press, London, New York, Paris, San Diego, San Francisco, Sao Paulo, Sydney, Tokyo, Toronto, 1982

    Google Scholar 

  110. Sloane, BF, Honn, KV, Sadler, JG, Turner, WA, Kimpson, JJ, Tayler, JD: Cathepsin B activity in B 16 melanoma cells: A possible marker for metastatic potential. Cancer Res 42: 980–986, 1982

    Google Scholar 

  111. Sträuli, P, Weiss, L: Cell locomotion and tumor penetration. Europ J Cancer 13: 1–12, 1977

    Google Scholar 

  112. Sträuli, P: A concept of tumor invasion. In: Sträuli, P, Barrett, AJ, Baici, A (eds): Proteinases and tumor invasion. Raven Press, New York, 1980, pp 1–5

    Google Scholar 

  113. Sträuli, P, Haemmerli, G, Tschenett, C, Krstic, RV: Different modes of mesenteric infiltration displayed by two rat leukemias. A study by scanning and transmission electron microscopy and by microcinematography. Virchows Arch B (Cell Pathol) 35: 93–108, 1981

    Google Scholar 

  114. Sträuli, P, Haemmerli, G: Cancer cell locomotion: its occurance during invasion. In: Mareel, MM, Calman, KC (eds): Invasion. Experimental and clinical implications. Oxford University Press, Oxford, New York, Tokyo, 1984, pp 252–274

    Google Scholar 

  115. Sugarbaker, EV, Weingrad, DN, Roseman, JM: Observations on cancer metastasis in man. In: Liotta, LA, Hart, IR (eds): Tumor invasion and metastasis. Martinus Nijhoff-Publishers, The Hague, Boston, London, 1982, pp 427–465

    Google Scholar 

  116. Suh, O, Weiss, L: The development of a technique for the morphometric analysis of invasion in cancer. J theor Biol 107: 547–561, 1984

    Google Scholar 

  117. Svennevig, JL, Holter, J: The local cell response to human lung carcinomas. Acta pathol microbiol Scand Sect A 89: 147–155, 1981

    Google Scholar 

  118. Svoboda, ELA, Deporter, DA: Phagocytosis of exogenous collagen by cultured murine fibroblasts and macrophages. A quantitative electron microscopic comparison. J Ultrastruct Res 72: 169–173, 1980

    Google Scholar 

  119. Sylven, B: Some factors relating to the invasiveness and destructiveness of solid malignant tumours. In: P, Denoix (ed): Mechanisms of invasion in cancer. Springer Verlag, Berlin, Heidelberg, 1967, pp 47–60

    Google Scholar 

  120. Takahashi, S, Konishi, Y, Nakatani, K, Inni, S, Kojima, K, Shiratori, T: Conversion of a poorly differentiated human adenocarcinoma to ascites form with invasion and metastasis in nude mice: Brief communication. J Natl Cancer Inst 60: 925–929, 1978

    Google Scholar 

  121. Tarin, D: Morphological studies on the mechanism of carcinogenesis. In: Tarin, D (ed): Tissue interactions in carcinogenesis. Academic Press, London, 1972, pp 227–290

    Google Scholar 

  122. Tarin, D, Hoyt, BJ, Evans, DJ: Correlation of collagenase secretion with metastatic-colonization potential in naturally occuring murine mammary tumours. Brit J Cancer 46: 266–278, 1982

    Google Scholar 

  123. Thorgeirsson, UP, Turpeeniemi-Hujanen, T, Neckers, LM, Johnson, DW, Liotta, LA: Protein synthesis but not DNA synthesis is required for tumor cell invasion in vitro. Invasion Metastasis 4: 73–83, 1984

    Google Scholar 

  124. Thynne, GS, Weiland, LH, Moertel, CG, Silvers, A: Correlation of histopathologic characteristics of primary tumor and uninvolved regional lymph nodes in Dukes' Class C colonic carcinoma with prognosis. Mayo Clin Proc 55: 243–245, 1980

    Google Scholar 

  125. Toh, BH, Muller, HK: Smooth muscle-associated antigen in experimental cutaneous squamous cell carcinoma, keratoacanthoma, and papilloma. Cancer Res 35: 3741–3745, 1975

    Google Scholar 

  126. Toole, BP, Trelstad, RL: Hyaluronate production and removal during corneal development in the chick. Develop Biol 26: 28–35, 1971

    Google Scholar 

  127. Tremblay, G, Babai, F: Intracellular junctions between Novikoff hepatoma cells and hepatic cells. Exp Cell Res 74: 355–358, 1972

    Google Scholar 

  128. Turcotte, H, Bazin, M, Boutet, M: Junctional complexes in regenerating endocardium. J Ultrastruct Res 79: 133–141, 1982

    Google Scholar 

  129. Underwood, JCE, Carr, I: The ultrastructure and permeability characteristics of the blood borne vessels of a transplantable rat sarcoma. J Path 107: 157–166, 1972

    Google Scholar 

  130. Van, Peteghem, MC, Mareel, MM, DeBruyne, GK: Phagocytic capacity of invasive malignant cells in three-dimensional culture. Virchows Arch B (Cell Pathol) 34: 193–204, 1980

    Google Scholar 

  131. Wang, T-Y, Nicolson, GL: Metastatic tumor cell invasion of brain organ tissue cultured on cellulose polyacetate strips. Clin Expl Metastasis 1: 327–339, 1983

    Google Scholar 

  132. Ward, JM: Morphogenesis of chemically induced neoplasms of the colon and small intestine in rats. Lab Invest 30: 505–513, 1974

    Google Scholar 

  133. Weber, K, Gröschel-Stewart, U: Antibody to myosin. The specific visualization of myosin-containing filaments in non-muscle cells. Proc Natl Acad Sci (Wash) 71: 4561–4564, 1974

    Google Scholar 

  134. Weiss, L, Ward, PM: Cell detachment and metastasis. Cancer Metast Rev 2: 111–127, 1983

    Google Scholar 

  135. Wiebecke, B, Krey, U, Löhrs, U, Eder, M: Morphological and autoradiographical investigations on experimental carcinogenesis and polyp development in the intestinal tract of rats and mice. Virchows Arch A (Pathologische Anatomie) 360: 197–193, 1973

    Google Scholar 

  136. Wiig, H, Tveit, E, Hultborn, R, Reed, RK, Weiss, L: Interstitial fluid pressure in DMBA-induced rat mammary tumours. Scand J clin Lab Invest 42: 159–164, 1982

    Google Scholar 

  137. Willis, RA: The spread of tumours in the human body (ed. RA, Willis) 3rd edition, Butterworths, London, 1973

    Google Scholar 

  138. WoodJr, S: Pathogenesis of metastasis formation observed in vivo in the rabbit ear chamber. AMA Arch Path 66: 550–568, 1958

    Google Scholar 

  139. Wood, S, Baker, RR, Marzocchi, B: In vivo studies of tumor behavior: locomotion and interrelationships between normal cells and cancer cells. In: Anderson tumor Institute (ed): The proliferation and spread of neoplastic cells. Williams and Wilkins, Baltimore, 1968, pp 495–509

    Google Scholar 

  140. Woolley, DE, Tetlow, LC, Mooney, CJ, Evanson, JM: Human collagenase and its extra-cellular inhibitors in relation to tumor invasiveness. In: Sträuli, P, Barrett, AJ, Baici, A (eds): Proteinases and tumor invasion. Raven Press, New York, 1980, pp 97–115

    Google Scholar 

  141. Woolley, DE: Proteolytic enzymes of invasive cells. In: Mareel, MM, Calman, KC (eds): Invasion. Experimental and clinical Implications. Oxford Univ Press, Oxford, New York, Tokyo, 1984, pp 228–251

    Google Scholar 

  142. Yamaura, H, Suzuki, M, Sato, H: Transparent chamber in the rat skin for studies on microcirculation in cancer tissue. Gann 62: 177–185, 1971

    Google Scholar 

  143. Young, JS: The invasive growth of malignant tumours: An experimental interpretation based on elastic-jelly models. J Path Bact 77: 321–339, 1959

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pathologisches Institut der Johannes Gutenberg, Universität Mainz, D-6500, Langenbeckstr. 1, Mainz, FRG

    Helmut Gabbert

Authors
  1. Helmut Gabbert
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gabbert, H. Mechanisms of tumor invasion: evidence from in vivo observations. Cancer Metast Rev 4, 293–309 (1985). https://doi.org/10.1007/BF00048094

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00048094

Key words

Search

Navigation