The role of IL-6, HGF and TGFβ_1 in biliary epithelial cells carcinogenesis

IL-6、HGF和TGFβ_1在胆管上皮细胞癌变中的作用

• 批准号: 12671275
• 负责人: YOKOMURO Shigeki
• 金额: $ 1.86万
• 依托单位: Nippon medical school
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671275/
• 关键词: cholangiocarcinoma; IL-6; HGF; TGFβ_1; TGFβ_1; 胆管上皮細胞癌; サイトカイン

Intraheptatic chollagiocarcinoma (CC) and other cancers of the biliary tree, including the gallbladder, are often associated with non-neoplastic inflammatory diseases of the biliary tree, such as sclerosing cholangitis, clonorchiasis, and hepatolithiasis. These diseases also involve reparative, non-neoplastic biliary epithelial cell (BEC) proliferation. Unfortunately, although a significant number of biliary tract cancers arise under predictable conditions, they carry a poor prognosis because of difficulties in establishing the diagnosis before the tumors reach a noncurative stage. Earlier diagnosis and attempts at curative therapy will require a better understanding of the molecular mechanisms controlling reparative and cancerous BEC growth and the steps involved in a transition between the 2 processes. During non-neoplastic BEC repair like that seen with obstructive cholangiopathy, competing mitogenic and mitoinhibitory influences action on BECs, largely in a paracrine fashion, are a … More ccompanied by activation of periductal myofibroblasts and fibrogenesis. For example, the first several days to weeks afte biliary obstraction are characterized by explosive BEC proliferation. This is associated with up-regulation of hepatocyte growth factor (HGF) and interleukin 6 (IL-6) in the peribiliary stromal and hematolymphoid cells, and these same mediators stimulate non-neoplastic BEC DNA synthesis, in vitro. However, if the obstruction persists, BEC proliferation returns to near beseline levels and progressive fibrogenesis ensues. This occurs coincidently with tht induction of mitoinhibitory and fibrogenic growth factors, such as fibroblast growth factor and the TGF-b family of mitoinhibitory cytokines, including TGF-b1 and activin A. Receptros for these mitogens or mitoinhibitors, respectivily, are upregulated on the sruface of the BEC during successive stages of the response. The transition from reactive BEC to CC is accompanied by alterations that favor continued growth over mitoinhibition and apoptosis. Thus, malignancies can circumvent the effect s of mediators that inhibit growth or induce apoptosis, or acquire the ability to synthesize and secrete their own growth factor(s), superseding the normal paractine signaling with autocrine pathways. Less

肝内胆管癌（CC）和胆管系统的其他癌症（包括胆囊）通常与胆管系统的非肿瘤性炎症性疾病相关，例如硬化性胆管炎、华支睾吸虫病和肝结石病。这些疾病还涉及修复性、非肿瘤性胆管上皮细胞（BEC）增殖。不幸的是，尽管大量胆道癌是在可预测的情况下发生的，但由于在肿瘤达到非治愈阶段之前很难做出诊断，因此它们的预后很差。早期诊断和尝试治愈性治疗需要更好地了解控制修复性和癌性 BEC 生长的分子机制以及这两个过程之间转换所涉及的步骤。在像阻塞性胆管病那样的非肿瘤性 BEC 修复过程中，竞争性促有丝分裂和有丝分裂抑制对 BEC 的作用（主要以旁分泌方式）伴随着导管周围肌成纤维细胞的激活和纤维化。例如，胆道梗阻后的最初几天到几周的特点是 BEC 爆炸性增殖。这与胆周基质细胞和造血淋巴细胞中肝细胞生长因子 (HGF) 和白细胞介素 6 (IL-6) 的上调有关，并且这些相同的介质在体外刺激非肿瘤性 BEC DNA 合成。然而，如果阻塞持续存在，BEC 增殖会恢复到接近基线水平，并随之发生进行性纤维化。这与有丝分裂抑制和成纤维生长因子的诱导同时发生，例如成纤维细胞生长因子和有丝分裂抑制细胞因子的 TGF-b 家族，包括 TGF-b1 和激活素 A。在反应的连续阶段，这些有丝分裂原或有丝分裂抑制剂的受体分别在 BEC 表面上调。从反应性 BEC 到 CC 的转变伴随着有利于持续生长而不是有丝分裂抑制和细胞凋亡的变化。因此，恶性肿瘤可以规避抑制生长或诱导细胞凋亡的介质的作用，或者获得合成和分泌自身生长因子的能力，用自分泌途径取代正常的旁腺信号传导。较少的

项目成果

Shigeki Yokomuro: "Growth Control of Human Biliary Epithelial Cells by IL-6, HGF, TGFB, and Activin A"Hepatology. 32. 26-35 (2000)

Shigeki Yokomuro：“IL-6、HGF、TGFB 和激活素 A 对人胆管上皮细胞的生长控制”肝病学。

Shigeki Yokomuro: "Growth Control of Human Biliary Epithelial Cells by IL-6, HGF, TGFβ_1 and Activin."Hepatology. 32. 26-35 (2000)

Shigeki Yokomuro：“IL-6、HGF、TGFβ_1 和激活素对人胆管上皮细胞的生长控制”，《肝病学》32. 26-35 (2000)。

Shigeki Yokomuro: "Growth Control of human biliary epithelial cells by IL-6 HGF, TGFβ1 and Activin A."Hepatology. 32(1). 26-35 (2000)

Shigeki Yokomuro：“IL-6 HGF、TGFβ1 和激活素 A 对人胆管上皮细胞的生长控制”，Hepatology 32(1) (2000)。