Growth control of human biliary epithelial cells by interleukin 6, hepatocyte growth factor, transforming growth factor β1, and activin A:: Comparison of a cholangiocarcinoma cell line with primary cultures of non-neoplastic biliary epithelial cells
Growth control of human biliary epithelial cells by interleukin 6, hepatocyte growth factor, transforming growth factor β1, and activin A:: Comparison of a cholangiocarcinoma cell line with primary cultures of non-neoplastic biliary epithelial cells
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DOI：
10.1053/jhep.2000.8535
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发表时间：
2000-07-01
期刊：
影响因子：
13.5
通讯作者：
Demetris, AJ
中科院分区：
文献类型：
--
作者：
Yokomuro, S;Tsuji, H;Demetris, AJ
比较了一种良好表征的人胆管癌（CC）细胞系SG 231与正常人胆管上皮细胞（BEC）原代培养物在白细胞介素6（IL-6）和肝细胞生长因子（HGF）介导的刺激以及转化生长因子β 1（TGF-β 1）和激活素A介导的生长抑制方面的变化。将结果与原始肿瘤的免疫标记以及将SG 231注射到BALB/cByJ-scid小鼠的肝脏中后的结果进行比较。在体外培养条件下，BEC和CC均表达Met、gp 80和gp 130 mRNA和蛋白，但CC的表达水平高于BEC。在CC和BEC中，外源性HGF或IL-6分别诱导met或gp 130磷酸化，并呈浓度依赖性增加DNA合成。然而，CC而不是BEC在基础无血清培养基（SFM）中继续生长，并在这些条件下自发产生IL-6和HGF，这分别导致gp 130和met的自身磷酸化;单独中和抗HGF或抗IL-6可抑制CC生长，表明自分泌生长控制回路。相反，激活素A抑制BEC和CC的生长，但不显著增加凋亡。激活素A诱导的CCs和BECs的生长抑制可被100 ng/mL的外源性IL-6逆转，但不能被10 - 100 ng/mL的HGF逆转。TGF-β 1抑制BECs的生长，但对CCs没有丝裂抑制或促凋亡作用。原始肿瘤和接种到scid小鼠后的免疫标记显示met、gp 130、gp 80和IL-6阳性染色。这项研究有助于进一步了解胆管癌发生过程中BEC的生长控制和紊乱。
A well characterized human cholangiocarcinoma (CC) cell line, SG231, was compared with primary cultures of normal human biliary epithelial cells (BECs) for alterations in interleukin 6 (IL-6) and hepatocyte growth factor (HGF)mediated stimulation and transforming growth factor pi (TGF-beta 1) and activin A-mediated inhibition of growth. Results were compared with immunolabeling of the original tumor and after injection of SG231 into the liver of BALB/cByJ-scid mice. In vitro, both BECs and CCs expressed met, gp80, and gp130 messenger RNA (mRNA) and protein, but the levels of expression were higher in the CCs than in the BECs. In both the CCs and BECs, exogenous HGF or IL-6 induced phosphorylation of met or gp130, respectively, and a concentration-dependent increase in DNA synthesis, However, the CCs but not BECs, continued to grow in basal serum-free medium (SFM) and spontaneously produced both IL-6 and HGF under these conditions, which resulted in auto-phosphorylation of gp130 and met, respectively; and neutralizing anti-HGF or anti-IL-6 alone inhibited CC growth, indicative of autocrine growth control circuits. Conversely, activin A inhibits the growth of both BECs and CCs, but does not significantly increase apoptosis. Activin-A-induced growth inhibition of both CCs and BECs can be reversed by 100 ng/mL exogenous IL-6, but not by 10 to 100 ng/mL HGF TGF-beta 1 inhibited the growth of BECs but had no mitoinhibitory or proapoptotic effects on CCs. Immunolabeling of the original tumor and after inoculation into scid mice showed positive staining for met, gp130, gp80, and IL-6. This study contributes to a further understanding of BEC growth control and derangements that can occur during cholangio carcinogenesis.