Geng Xinglong, Chen Hongze, Zhao Liang, Hu Jisheng, Yang Wenbo, Li Guanqun, Cheng Chundong, Zhao Zhongjie, Zhang Tao, Li Le, Sun Bei
Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Front Cell Dev Biol. 2021 Jul 15;9:655152. doi: 10.3389/fcell.2021.655152. eCollection 2021.
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease that typically features a dramatic desmoplastic reaction, especially fibroblasts. The roles of cancer-associated fibroblasts (CAFs) in PDAC have received more attention in recent years. As increasing evidence suggests the heterogeneity of CAFs in PDAC, different CAF subtypes have been shown to support tumor growth, while others suppress cancer proliferation. Myofibrotic CAFs (myCAFs) show alpha-smooth muscle actin (α-SMA) interleukin-6 (IL-6) myofibroblastic features, are activated by direct contact with tumor cells, and are located in the periglandular region. Inflammatory CAFs (iCAFs) show α-SMA IL-6 inflammatory features, are activated by paracrine factors secreted from tumor cells, and are located away from cancer cells. Antigen-presenting CAFs (apCAFs) show major histocompatibility complex II (MHC II) family genes that are highly expressed. CAFs have also been gradually explored as diagnostic and prognostic markers in pancreatic cancer. Targeted therapy of CAFs in PDAC has gradually attracted attention. With the deepening of related studies, some meaningful positive and negative results have surfaced, and CAFs may be the key to unlocking the door to pancreatic cancer treatment. Our review summarizes recent advances in the heterogeneity, function, and markers of CAFs in pancreatic cancer, as well as research and treatment targeting CAFs in pancreatic cancer.
胰腺导管腺癌（PDAC）是一种致死率很高的疾病，其典型特征是有显著的促纤维增生反应，尤其是成纤维细胞方面。近年来，癌症相关成纤维细胞（CAFs）在PDAC中的作用受到了更多关注。越来越多的证据表明PDAC中CAFs具有异质性，不同的CAF亚型已被证明可支持肿瘤生长，而其他亚型则抑制癌症增殖。肌成纤维细胞性CAFs（myCAFs）表现出α平滑肌肌动蛋白（α-SMA）、白细胞介素-6（IL-6）和肌成纤维细胞特征，通过与肿瘤细胞直接接触而被激活，且位于腺周区域。炎性CAFs（iCAFs）表现出α-SMA、IL-6和炎性特征，由肿瘤细胞分泌的旁分泌因子激活，且位于远离癌细胞的位置。抗原呈递CAFs（apCAFs）表现出高表达的主要组织相容性复合体II（MHC II）家族基因。CAFs也已逐渐被探索作为胰腺癌的诊断和预后标志物。PDAC中针对CAFs的靶向治疗已逐渐引起关注。随着相关研究的深入，一些有意义的阳性和阴性结果浮出水面，CAFs可能是打开胰腺癌治疗大门的关键。我们的综述总结了胰腺癌中CAFs的异质性、功能和标志物的最新进展，以及针对胰腺癌中CAFs的研究和治疗情况。
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