Comparative tumor morphogenesis of two human colon adenocarcinoma cell clones xenografted in the immunosuppressed newborn rat.
Two clones derived from the human adenocarcinoma cell line LoVo, E2 and C5 xenografted subcutaneously to immunosuppressed newborn rats, respectively produced well-differentiated and undifferentiated tumors. The comparative morphogenesis of these tumors was performed on xenografts explanted as early as 18 h and up to 21 days after grafting by studying the progressive setting of the enterocyte differentiation marker dipeptidylpeptidase IV, the basal lamina component laminin and the alpha 6 integrin subunit. E2 xenografts which were entirely undifferentiated 18 h after grafting, presented well-polarized acini-like tumoral islets 6 h later, i.e. only 1 day after injection. Basement membranes, which were not organized at this moment, may not be necessary for morphological polarization. The chronology of function antigens polarization was characterized by formation of a basement membrane 5 days after the graft with associated basal sorting of alpha 6 integrin. The polarization of alpha 6 integrin took, however, longer to be achieved while apical addressing of dipeptidylpeptidase IV was the last to be completed. In contrast, C5 tumors never differentiated. Even 21 days after grafting alpha 6 integrin remained pericellular, dipeptidylpeptidase IV was underexpressed and laminin was found as perilobular patches. Quantitative differences in laminin or alpha 6 integrin expression could not account for the differences in the polarization process observed in the two variants.