COLON-CANCER CELL VARIANTS PRODUCING REGRESSIVE TUMORS IN SYNGENEIC RATS, UNLIKE VARIANTS YIELDING PROGRESSIVE TUMORS, ATTACH TO INTERSTITIAL COLLAGENS THROUGH INTEGRIN ALPHA(2)BETA(1)

Nine clones of tumor cells, derived from a single rat colon carcinoma, were analyzed for their adhesive properties and in vivo growth patter ns. Four clones (denoted REG) gave rise to regressively growing tumors . Cells from the 4 REG clones attached significantly better to collage n types I and III than did cells from the 5 clones (denoted PRO) which grew progressively in vivo. In contrast, REG and PRO clones did not d iffer in their attachment to collagen type IV, laminin or fibronectin. The attachment of REG cells to collagen was dependent on Mg2+, but no t Ca2+. Monospecific rabbit IgG to rat integrin beta(1)-chain inhibite d REG cell attachment to collagen, demonstrating involvement of a beta (1) integrin in this process. PRO and REG cells expressed an underglyc osylated beta(1) chain (M(r) similar to 105,000) that was somewhat sma ller than beta(1)-chains described previously on vat fibroblasts and h epatocytes (M(r) similar to 115,000). Monoclonal IgG to rat integrin a lpha(2) beta(1), but not to alpha(1) beta(1), readily inhibited REG ce ll attachment to collagen, demonstrating the involvement of integrin a lpha(2) beta(1). However, beta(1) and alpha(2) integrin subunits were found in purified glycoproteins from both PRO and REG cells. This sugg ests that alpha(2) beta(1) integrin is expressed by both cell variants , but is functional as a collagen receptor on REG cells only. In this system of tumor-cell variants, the clear-cut differences in attachment to interstitial collagens of the 9 clones suggest a possible relation ship between this attachment and the capacity to induce progressive or regressive tumors. (C) 1996 Wiley-Liss, Inc.