Pignatelli M, Bodmer W F
Director's Laboratory, Imperial Cancer Research Fund, London, United Kingdom.
Proc Natl Acad Sci U S A. 1988 Aug;85(15):5561-5. doi: 10.1073/pnas.85.15.5561.
We have examined the interaction between collagen binding and epithelial differentiation by using a human colon carcinoma cell line (SW1222) that can differentiate structurally when grown in a three-dimensional collagen gel to form glandular structures. As much as 66% inhibition of glandular differentiation can be achieved by addition to the culture of a synthetic peptide (2 mg/ml) containing the Arg-Gly-Asp-Thr (RGDT) sequence, which is a cell recognition site found in collagen. Arg-Gly-Asp-Thr also inhibited the cell attachment to collagen-coated plates. A control peptide containing the Arg-Gly-Glu-Thr (RGET) sequence had no effect on cell adhesion or cell differentiation. Chromosome 15 was found in all human-mouse hybrid clones [from a cross between SW1222 and a mouse rectal carcinoma cell line (CMT-93)] that could differentiate in the collagen gel and bind collagen. Both binding to collagen and glandular differentiation of the hybrid cells were also inhibited by Arg-Gly-Asp-Thr as for the parent cell line SW1222. The ability of SW1222 cells to express the differentiated phenotype appears, therefore, to be determined by an Arg-Gly-Asp-directed collagen receptor on the cell surface that is controlled by a gene on chromosome 15.
我们利用一种人结肠癌细胞系（SW1222）研究了胶原蛋白结合与上皮分化之间的相互作用。当该细胞系在三维胶原蛋白凝胶中生长时，能够在结构上分化形成腺状结构。向培养物中添加一种含有精氨酸 - 甘氨酸 - 天冬氨酸 - 苏氨酸（RGDT）序列的合成肽（2毫克/毫升），可实现高达66%的腺状分化抑制，RGDT序列是胶原蛋白中发现的细胞识别位点。RGDT也抑制细胞与胶原蛋白包被平板的附着。一种含有精氨酸 - 甘氨酸 - 谷氨酸 - 苏氨酸（RGET）序列的对照肽对细胞黏附或细胞分化没有影响。在所有能够在胶原蛋白凝胶中分化并结合胶原蛋白的人 - 小鼠杂交克隆（来自SW1222与小鼠直肠癌细胞系CMT - 93的杂交）中都发现了15号染色体。与亲本细胞系SW1222一样，RGDT也抑制杂交细胞与胶原蛋白的结合以及腺状分化。因此，SW1222细胞表达分化表型的能力似乎由细胞表面一种由15号染色体上的基因控制的、以RGDT为导向的胶原蛋白受体所决定。
