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

Abstract

Expression of the 37-kDa laminin binding protein (37LBP/p40), a precursor of the 67-kDa laminin receptor, is well-correlated with the biological aggressiveness 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 expression 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 transfectant with vehicle only (40 h). In-vitro studies also showed that T11 cells adhered 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 prolonged 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 tissue revealed that T11 cells were loosely apposed and their intercellular space was markedly widened. Some of the T11 cells sporadically degenerated with the infiltration of lymphocytes and neutrophils. These results suggest that the suppressed expression of 37LBP/p40 reduces the capability of lung cancer cell proliferation in vitro and tumour formation in vivo.