Butyrate downregulates α2β1 integrin:: a possible role in the induction of apoptosis in colorectal cancer cell lines
Butyrate downregulates α2β1 integrin:: a possible role in the induction of apoptosis in colorectal cancer cell lines
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DOI：
10.1136/gut.52.5.729
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发表时间：
2003-05-01
期刊：
影响因子：
24.5
通讯作者：
Pignatelli, M
中科院分区：
文献类型：
--
作者：
Buda, A;Qualtrough, D;Pignatelli, M
背景：整合素介导细胞基质粘附并调节细胞生长和存活。在结肠上皮细胞中，α(2)β(1) 整合素控制腺体分化和增殖。丁酸盐在体外刺激分化并诱导细胞凋亡。目的：我们研究了丁酸盐诱导细胞凋亡是否与整合素介导的细胞基质粘附的扰动相关。方法：研究了三种结肠癌细胞系（SW1222、SW620、LS174T）。研究了用 4 mM 丁酸盐处理后贴壁细胞对细胞外基质蛋白的粘附、α(2)β(1) 整合素的表达和细胞凋亡。结果：丁酸盐减少了 SW620 细胞中 I 型胶原蛋白以及 LS174T 细胞中 I 型和 IV 型胶原蛋白的粘附。细胞附着减少与α(2)β(1)整合素下调和贴壁细胞凋亡增加有关。在 SW1222 细胞中未观察到 α(2)β(1) 表达或基质粘附的变化，并且还发现该细胞对丁酸盐诱导的细胞凋亡不太敏感。 α(2)β(1)整合素的下调先于细胞凋亡的检测。结论：丁酸盐诱导的细胞凋亡与α(2)β(1)整合素表达和功能活性的下调有关。细胞基质粘附的扰动可能是丁酸盐诱导结直肠癌细胞凋亡的新机制。
Background: Integrins mediate cell matrix adhesion and regulate cell growth and survival. In colonic epithelial cells, alpha(2)beta(1) integrin controls glandular differentiation and proliferation. Butyrate stimulates differentiation and induces apoptosis in vitro.Aims: We investigated whether butyrate induction of apoptosis was associated with perturbation of integrin mediated cell matrix adhesion.Methods: Three colonic cancer cell lines (SW1222, SW620, LS174T) were studied. Adhesion to extracellular matrix proteins, expression of alpha(2)beta(1) integrin, and apoptosis were studied in adherent cells after treatment with 4 mM butyrate.Results: Butyrate decreased the attachment to type I collagen in SW620 cells and type I and IV collagen in LS174T cells. The decreased cell attachment was associated with downregulation of alpha(2)beta(1) integrin and increased apoptosis in adherent cells. No changes in alpha(2)beta(1) expression or matrix adhesion were seen in SW1222 cells, which were also found to be less sensitive to butyrate induction of apoptosis. Downregulation of alpha(2)beta(1) integrin preceded the detection of apoptosis.Conclusion: Apoptosis induced by butyrate is associated with downregulation of expression and functional activity of alpha(2)beta(1) integrin. Perturbation of cell matrix adhesion may be a novel mechanism by which butyrate induces apoptosis in colorectal cancer cells.