Diminution of 37-kDa laminin binding protein expression reduces tumour formation of murine lung cancer cells

Expression of the 37-kDa laminin binding protein (37LBP/p40), a precursor o f the 67-kDa laminin receptor, is well-correlated with the biological aggre ssiveness of cancer cells. To elucidate the direct role played by 37LBP/p40 in cancer cells, a murine lung cancer cell line T11, the 37LBP/p40 express ion of which was remarkably diminished, was established by the introduction of the antisense 37LBP/p40-RNA using a retroviral vector. As a result, the population doubling time of T11 was prolonged (60 h) compared with that of P29, the non-transfected parental cell line (42 h), and TN2, a transfectan t with vehicle only (40 h). In-vitro studies also showed that T11 cells adh ered to immobilized laminin less firmly than P29 cells did. When 5 x 10(5) cells were subcutaneously inoculated into syngenic mice, the mean survival time of T11-recipients (77.0 +/- 14.8 days) was also significantly prolonge d compared with that for P29 (34.8 +/- 5.5 days) and TN2 (36.7 +/- 6.1 days ) recipients (P < 0.001). The electron-microscopic view of the tumour tissu e revealed that T11 cells were loosely apposed and their intercellular spac e was markedly widened. Some of the T11 cells sporadically degenerated with the infiltration of lymphocytes and neutrophils. These results suggest tha t the suppressed expression of 37LBP/p40 reduces the capability of lung can cer cell proliferation in vitro and tumour formation in vivo.