Abstract
Scirrhous carcinoma of the stomach is characterized by rapid growth with a vast fibrous stroma, high invasiveness, and substantially a poor prognosis. Little is known of the molecular pathogenesis of this disease. Members of the emerging family of the CCN gene (for connective tissue growth factor, cysteine-rich 61, nephroblastoma overexpressed) encode cysteine-rich secreted proteins with roles in human fibrotic disorders and cancer progression. Using targeted differential displays, we identified a novel variant of the CCN family member WISP1 (Wnt-induced secreted protein 1), named WISP1v, as overexpressed in scirrhous gastric carcinomas. Predicted protein of the WISP1v completely lacks a module of Von Willebrand type C that is thought to participate in protein complex formation. Ectopic expression revealed WISP1v to be a secreted oncoprotein inducing a striking cellular transformation and rapid piling-up growth. It is noteworthy that WISP1v transfectants enhanced the invasive phenotype of co-cultured gastric carcinoma cells, while wild-type WISP1 had no such potential. These findings suggest that CCN protein WISP1v is involved in the aggressive progression of scirrhous gastric carcinoma.
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Acknowledgements
We thank Dr Dianne Pennica (Genetech Inc.) and Prof Jack R Wands (Brown University) for helpful discussions; and Ms M Hirata and M Kubota for technical assistance. This work was supported by NOVARTIS Foundation for the Promotion of Science, Sagawa Cancer Research Fund, Fukuoka Cancer Research Foundation, and Grant-in-Aid from the Ministry of Education, Science, Technology, Sports and Culture of Japan. S Tanaka is a recipient of the Japan Cancer Society Incitement Award.
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Tanaka, S., Sugimachi, K., Saeki, H. et al. A novel variant of WISP1 lacking a Von Willebrand type C module overexpressed in scirrhous gastric carcinoma. Oncogene 20, 5525–5532 (2001). https://doi.org/10.1038/sj.onc.1204723
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DOI: https://doi.org/10.1038/sj.onc.1204723
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