ORGANIZATION AND GEL CONTRACTION BY HUMAN COLONIC-CARCINOMA (HCA-7) SUBLINES GROWN IN 3-DIMENSIONAL COLLAGEN GEL

The role of cell-matrix interactions in controlling phenotypic heterog eneity in human colonic carcinoma sublines has been investigated. Four cell lines (colony 1, colony 3, colony 6 and colony 30) previously is olated from a single human colonic carcinoma cell line, HCA-7, were gr own in 3-dimensional collagen gels. In collagen, the growth of the 4 s ublines ranged from well-organised glandular structures (colony 30) to elongated branching structures (colony 3). The capability of cells to organise into glandular structures in collagen correlated with the de gree of differentiation observed in their xenografts. Certain sublines , most notably colony 3, were able to contract the collagen gel. Gel c ontraction could be partially inhibited by a function-blocking antibod y directed to the alpha(2) integrin chain but not by an antibody direc ted to the alpha(3) integrin chain demonstrating a role for alpha(2) i ntegrin in the contraction process. In addition, colony 3 cultures tre ated with the function-blocking alpha(2) antibody formed more compact structures with limited outgrowth, suggesting a role for alpha(2) inte grin in cell migration. Gel contraction and cell migration in collagen gel was largely restricted to I subline, colony 3. The subsequent dem onstration that alpha(2) integrin is involved in both of these process es suggests that integrin expression and function has a role in genera ting the phenotypic heterogeneity exhibited by these cell lines. (C) 1 995 Wiley-Liss, Inc.