Zvibel I, Brill S, Halpern Z, Papa M
Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Weizman 6, Tel Aviv, Israel.
Exp Cell Res. 1998 Nov 25;245(1):123-31. doi: 10.1006/excr.1998.4229.
We investigated the role of hepatocyte extracellular matrix (ECM) on the growth of human colon cancer cell lines. We cultured four cell lines with different liver-colonizing potential on ECM derived from primary rat hepatocyte cultures. We investigated the effect of ECM on cell proliferation, clonal growth, and expression of growth factors and growth factor receptors. The highly metastatic cells showed better clonal growth and produced larger colonies on ECM. The proliferation of all colon cancer cell lines was enhanced on hepatocyte ECM, yet inhibited on fibroblast ECM. Screening of autocrine growth factors and receptors showed that the cells expressed growth factors and receptors of the EGF family: EGF receptor, erb-B2, amphiregulin, and cripto. The expression of cripto mRNA, but not of amphiregulin, was induced in KM12SM cells grown on ECM. All colon cancer cell lines grown on ECM showed increased expression of erb-B2. The effect of ECM on erb-B2 expression was mediated by the heparin chains of heparin proteoglycan. ECM from hepatocytes grown in the presence of nitrophenyl-beta-D-xylopyrannoside or sodium chlorate, which prevent formation of heparin proteoglycan, as well as ECM treated with heparinase, had no effect on erb-B2 expression. Our studies suggest a role for liver ECM as a determinant of colon cancer metastasis. Liver ECM acts, in part, via induction of members of the EGF family of growth factors and their receptors.
我们研究了肝细胞外基质（ECM）对人结肠癌细胞系生长的作用。我们将四种具有不同肝定植潜力的细胞系培养在源自原代大鼠肝细胞培养物的ECM上。我们研究了ECM对细胞增殖、克隆生长以及生长因子和生长因子受体表达的影响。高转移性细胞在ECM上表现出更好的克隆生长并形成更大的集落。所有结肠癌细胞系在肝细胞ECM上的增殖均增强，但在成纤维细胞ECM上受到抑制。对自分泌生长因子和受体的筛选表明，这些细胞表达表皮生长因子（EGF）家族的生长因子和受体：EGF受体、erb-B2、双调蛋白和cripto。在ECM上生长的KM12SM细胞中，cripto mRNA的表达被诱导，而双调蛋白的表达未被诱导。所有在ECM上生长的结肠癌细胞系erb-B2的表达均增加。ECM对erb-B2表达的影响是由肝素蛋白聚糖的肝素链介导的。在硝基苯基-β-D-吡喃木糖苷或氯酸钠存在下生长的肝细胞的ECM，这两种物质可阻止肝素蛋白聚糖的形成，以及用肝素酶处理的ECM，对erb-B2表达均无影响。我们的研究表明肝脏ECM作为结肠癌转移的决定因素发挥作用。肝脏ECM部分通过诱导EGF家族生长因子及其受体的成员发挥作用。
