Bile acids stimulate invasion and haptotaxis in human colorectal cancer cells through activation of multiple oncogenic signaling pathways
Bile acids stimulate invasion and haptotaxis in human colorectal cancer cells through activation of multiple oncogenic signaling pathways
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DOI：
10.1038/sj.onc.1205729
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发表时间：
2002-10-03
期刊：
影响因子：
8
通讯作者：
Mareel, MM
中科院分区：
文献类型：
--
作者：
Debruyne, PR;Bruyneel, EA;Mareel, MM
流行病学和实验研究表明，胆汁酸与结直肠癌发生有关。我们研究了在肿瘤进展的不同阶段，胆汁酸是否刺激人结直肠和狗肾上皮细胞的细胞侵袭。将结肠PC/AA/C1、PCmsrc和HCT-8/E11细胞和肾MDCKT 23细胞接种在I型胶原凝胶上，孵育24小时后计数侵袭细胞。Rac 1和RhoA小GTP酶的激活通过下拉测定进行了研究。用改良的Boyden小室分析趋触性。石胆酸、鹅脱氧胆酸、胆酸和脱氧胆酸刺激SRC和RhoA转化的PCmsrc和MDCKT 23-RhoAV 14细胞以及来自散发性肿瘤的HCT-8/E11细胞的细胞侵袭，但对癌前PC/AA/C1和MDCKT 23细胞无效。胆汁酸刺激的入侵发生通过刺激的haptotaxis和依赖于RhoA/Rho-激酶途径和信号级联使用蛋白激酶C，促分裂原活化蛋白激酶，环氧合酶-2。因此，BA诱导的侵袭与Rac 1和RhoA GTP酶的激活和法尼醇X受体的表达有关。我们的结论是，胆汁酸刺激大肠癌细胞的侵袭和趋触性，通过几个癌症侵袭信号通路。
Bile acids are implicated in colorectal carcinogenesis as evidenced by epidemiological and experimental studies. We examined whether bile acids stimulate cellular invasion of human colorectal and dog kidney epithelial cells at different stages of tumor progression. Colon PC/AA/C1, PCmsrc, and HCT-8/E11 cells and kidney MDCKT23 cells were seeded on top of collagen type I gels and invasive cells were counted after 24 h incubation. Activation of the Rac1 and RhoA small GTPases was investigated by pull-down assays. Haptotaxis was analysed with modified Boyden chambers. Lithocholic acid, chenodeoxycholic acid, cholic acid and deoxycholic acid stimulated cellular invasion of SRC-and RhoA-transformed PCmsrc and MDCKT23-RhoAV14 cells, and of HCT-8/E11 cells originating from a sporadic tumor, but were ineffective in premalignant PC/AA/C1 and MDCKT23 cells. Bile acid-stimulated invasion occurred through stimulation of haptotaxis and was dependent on the RhoA/Rho-kinase pathway and signaling cascades using protein kinase C, mitogen-activated protein kinase, and cyclooxygenase-2. Accordingly, BA-induced invasion was associated with activation of the Rac1 and RhoA GTPases and expression of the farnesoid X receptor. We conclude that bile acids stimulate invasion and haptotaxis in colorectal cancer cells via several cancer invasion signaling pathways.