Suppression of laminin binding protein (37LBP/p40) expression affects angiogenesis in the murine lung tumor

Expression of the 37-kDa laminin binding protein (37LBP/p40), a precursor of the 67-kDa laminin receptor, is well correlated with biological aggressiveness of cancer cells. Details of the role of 37LBP/p40 are, however, not fully understood. To elucidate the role played by the 37LBP/p40 in cancer cells directly, a murine lung cancer cell line T11, the 37LBP/p40 expression of which was remarkably decreased, was established by introduction of the antisense 37LBP/p40 RNA by using a retroviral vector. As a result, the population doubling time of T11 was prolonged (60 h), compared with those of P29, non-transfected cell line (42 h) and TN2, a transfectant with vehicle only (40 h). When 5 x 10 ⁵ cells were subcutaneously injected into syngenic mice, the mean survival time of the T11 recipient (77.0±14.8 days) was also significantly prolonged compared with those of P29 (34.8±5.5 days) and TN2 (36.7±6.1 days), (p<0.001). Immunohistochemistry demonstrated that the density of microvessels in the T11 tumor was lower than those in P29 and TN2 tumor (p<0.05). It was also shown that conditioned medium of T11 cells induced capillary endothelial cell migration less than those of P29 and T42 sense RNA-transfectant did (p<0.05). These results suggest that decreased expression of 37LBP/p40 may relate to low tumorigenicity and that this may be partly caused by affected neovascularization of the murine lung cancer.