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Suppression of Transformed Phenotypes of Human Fibrosarcoma Cells by Overexpression of Recombinant Fibronectin¹

Research Institute, Osaka Medical Center for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka 590-02 [H. A., K. I-T., K. O., K. S.]; Department of Surgery, Osaka University Medical School, Suita, Osaka 565 [H. A., W. K., H. M.]; and Institute for Comprehensive Medical Science, Funjita Health University, Toyoake, Aichi 470-11 [K. I-T.], Japan

Loss of fibronectin (FN) from the cell surface has been shown to be closely associated with malignant transformation of cells. To elucidate the role of the FN matrix in the modulation of malignant phenotypes, we overexpressed a full-length cDNA encoding plasma-type FN in HT1080 human fibrosarcoma cells. The cells overexpressing FN adopted a more flattened morphology and deposited a moderately developed FN matrix both in vitro and in vivo, although the level of expression of integrin 5ß1 remained unchanged. FN-overexpressing cells exhibited a reduced cell motility on the substratum and grew poorly when injected s.c. into nude mice. Overexpression of FN also suppressed the ability of the tumor cells to proliferate in soft agar, whereas the suppression was reversed by inclusion in soft agar of the Arg-Gly-Asp (RGD)-containing peptide and adhesion-blocking antibodies against the central cell-binding domain of FN. Neither cell motility nor growth potential was altered by overexpression of a truncated form of FN lacking the central cell-binding domain. These results, taken together, indicate that increased deposition of FN in the pericellular matrix per se can suppress the motility and growth potential of tumor cells through interaction with RGD-recognizing integrins, most likely 5ß1.

¹ This work was supported by Special Coordination Funds from the Science and Technology Agency of Japan and a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, and Culture of Japan.

² To whom requests for reprints should be addressed.

Received 4/25/96. Accepted 7/31/96.

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