PO.TB10.11 · 肿瘤生物学

癌症相关成纤维细胞在胰腺癌和胆道癌中的不同作用——癌症相关成纤维细胞作为胆道癌中的肿瘤抑制因子

Different roles of cancer-associated fibroblasts in pancreatic cancer and biliary tract cancers cancer-associated fibroblasts as a tumor suppressor in biliary tract cancers

编号 6033 展板 10 时间 4/21 02:00–05:00 区域 Section 25 主讲 Ryota Tanaka, MD;PhD

分会场 Fibroblasts as Architects of the Tumor Microenvironment

该海报暂无可下载的资料 AACR 官方页面

作者与单位 Authors & Affiliations

Ryota Tanaka, Kenjiro Kimura, Naoki Tani, Shimpei Eguchi, Daisuke Inoue, Takuto Yasuda, Changgi Ahn, Koichi Nakanishi, Kosuke Hatta, Shigeaki Kurihara, Jun Tauchi, Sadaaki Nishimura, Masahiko Kinoshita, Kohei Nishio, Hiroji Shinkawa, Takeaki Ishizawa

Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan

摘要 Abstract

中文摘要

背景和目的：癌症相关成纤维细胞（CAFs）是肿瘤微环境的主要组成部分，可表现出促癌功能；然而，近期研究表明CAFs也可抑制癌症生长和进展。在本研究中，我们鉴定了在胆道癌中发挥抑制作用的CAFs，并阐明了其机制。材料与方法：我们回顾性评估了1996年至2017年在本机构接受手术治疗的114例胰腺导管癌（PDAC）和154例胆道癌（BTCs）的CAFs中alpha-平滑肌肌动蛋白（alphaSMA）的表达。使用从BTC和PDAC切除标本中分离的BTC细胞系、PDAC细胞系和CAFs来评估癌细胞的增殖潜能。从CAFs制备条件培养基（CM）（CM-CAF）。对CM-CAFs进行蛋白芯片分析，以鉴定负责生长抑制的候选因子。结果：alphaSMA表达阳性的PDAC患者的总生存期和无复发生存期显著短于alphaSMA阴性患者（分别为p = 0.003，p = 0.009）。另一方面，alphaSMA表达阳性的BTC患者的无复发生存期优于alphaSMA阴性患者（p = 0.03）。CM-CAF仅在BTC癌细胞系中抑制癌细胞增殖，而在PDAC细胞系中则不然。CM-CAFs的蛋白芯片显示，IL-6和IL-8是抑制BTC癌细胞增殖的关键抑制因子。中和IL-6和IL-8后，对BTC细胞增殖的抑制作用被消除。结论：CAFs在BTC中是有利的预后因素，但在PDAC中则不然。我们证明了BTC中存在肿瘤抑制性CAFs，它们通过分泌IL-6和IL-8发挥抗增殖作用。这些发现提示CAFs在胆道癌肿瘤微环境中具有一种新颖的、依赖于环境的作用。

查看英文原文 English abstract

Background and aims: Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment and can exhibit cancer-promoting functions; however, recent studies indicate that CAFs can also inhibit cancer growth and progression. In this study, we identified CAFs that act in an inhibitory manner in biliary tract cancer and elucidated their mechanisms. Materials and Methods: We retrospectively evaluated alpha-smooth muscle actin (alphaSMA) expression in CAFs from 114 cases of pancreatic ductal carcinoma (PDAC) and 154 cases of biliary tract cancers (BTCs) who underwent surgical treatment at our institution from 1996 to 2017. The BTC cell lines, PDAC cell lines, and CAFs were isolated from resected specimens of BTC and PDAC were used to evaluate the proliferative potential of cancer cells. Conditioned media (CM) were prepared from CAFs (CM-CAF). Protein array analysis of CM-CAFs was conducted to identify candidate factors responsible for growth suppression. Results: PDAC patients with positive alphaSMA expression showed significantly shorter overall survival and recurrence-free survival than alphaSMA-negative patients (p = 0.003, p = 0.009, respectively). On the other hands, BTC patients with positive alphaSMA expression showed better recurrence-free survival than alphaSMA-negative patients (p = 0.03). CM-CAF suppressed the proliferation of cancer cells only in BTC cancer cell lines, not in PDAC cell lines. Protein arrays of CM-CAFs revealed that IL-6 and IL-8 were key suppressive factors on BTC cancer cell proliferation. The inhibitory effects on BTC cell proliferation were abolished upon neutralization of IL-6 and IL-8. Conclusions: CAFs serve as a favorable prognostic factor in BTC but not in PDAC. We demonstrated the presence of tumor-suppressive CAFs in BTC, which exert their anti-proliferative effects through the secretion of IL-6 and IL-8. These findings suggest a novel, context-dependent role for CAFs in the tumor microenvironment of biliary tract cancers.

利益披露 Disclosure

R. Tanaka, None.. K. Kimura, None.. N. Tani, None.. S. Eguchi, None.. D. Inoue, None.. T. Yasuda, None.. C. Ahn, None.. K. Nakanishi, None.. K. Hatta, None.. S. Kurihara, None.. J. Tauchi, None.. S. Nishimura, None.. M. Kinoshita, None.. K. Nishio, None.. H. Shinkawa, None.. T. Ishizawa, None.

← 返回 AACR 2026 检索