Organisation and gel contraction by human colonic carcinoma (HCA‐7) sublines grown in 3‐dimensional collagen gel

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Abstract
The role of cell-matrix interactions in controlling phenotypic heterogeneity in human colonic carcinoma sublines has been investigated. Four cell lines (colony 1, colony 3, colony 6 and colony 30) previously isolated from a single human colonic carcinoma cell line, HCA-7, were grown in 3-dimensional collagen gels. In collagen, the growth of the 4 sublines 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 degree of differentiation observed in their xenografts. Certain sublines, most notably colony 3, were able to contract the collagen gel. Gel contraction could be partially inhibited by a function-blocking antibody directed to the α2 integrin chain but not by an antibody directed to the α3 integrin chain demonstrating a role for α2 integrin in the contraction process. In addition, colony 3 cultures treated with the function-blocking α2 antibody formed more compact structures with limited outgrowth, suggesting a role for α2 integrin in cell migration. Gel contraction and cell migration in collagen gel was largely restricted to 1 subline, colony 3. The subsequent demonstration that α2 integrin is involved in both of these processes suggests that integrin expression and function has a role in generating the phenotypic heterogeneity exhibited by these cell lines.

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