Stimulation of cellular growth and adhesion to fibronectin and vitronectinin culture and tumorigenicity in nude mice by overexpression of trypsinogen in human gastric cancer cells

It has previously been reported that the trypsinogen gene is expressed in v arious human cancers. To investigate the possible role of trypsin in tumor malignancy, trypsinogen-l cDNA was introduced into the human gastric carcin oma cell line MKN-1, The overexpression of trypsinogen-l in MKN-1 cells sti mulated cellular growth and adhesion to fibronectin and vitronectin when th e trypsinogen activator enterokinase was added into the culture, Enterokina se treatment of the conditioned medium of the MKN-1 transfectants partially converted the proforms of gelatinases B and A to their apparent active for ms, When the MKN-1 transfectants expressing trypsinogen-l were intraperiton eally transplanted into nude mice, the mice frequently produced tumors in t he colon, spleen and liver. However, the mice implanted with control MKN-1 cells produced no tumors. These results strongly suggest that tumor-derived trypsin contributes to the disseminated growth of some types of cancer cel ls including gastric cancer.