The role of stromal cancer-associated fibroblasts in pancreatic cancer.
The role of stromal cancer-associated fibroblasts in pancreatic cancer.
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DOI：
10.1186/s13045-017-0448-5
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发表时间：
2017-03-28
影响因子：
28.5
通讯作者：
Verma A
中科院分区：
文献类型：
--
作者：
von Ahrens D;Bhagat TD;Nagrath D;Maitra A;Verma A
胰腺导管腺癌（PDAC）是一种常规治疗难以治愈的致死性癌症。癌症相关成纤维细胞（CAFs）是肿瘤特有的促结缔组织间质的细胞成分，有助于这种治疗抵抗。包括钯和CD146在内的各种caf标志物在PDAC的病理生物学中具有预后和功能作用。cafa -肿瘤细胞相互作用的机制包括外泌体转移和由GM-CSF和IL-6等细胞因子介导的旁分泌信号传导。下游信号通路包括JAK/STAT、mTOR、SHH和NFkB也被证明在PDAC-CAF串扰中发挥重要作用。自噬和其他代谢作用对肿瘤内各细胞类型的作用也被提出在低糖微环境中促进CAF分泌功能和促进肿瘤生长。针对间质的多个临床前和临床试验已经引起了人们的兴趣，这些试验针对SHH、JAK2，以及利用CAFs的分泌能力来增强药物传递或抑制其以防止其对癌细胞化疗耐药的影响的方法。本文综述了在理解基质形成方面的最新进展；它对肿瘤增殖、侵袭和转移的作用；它在化学耐药中的作用；以及潜在的治疗策略。
Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer generally refractory to conventional treatments. Cancer-associated fibroblasts (CAFs) are cellular components of the desmoplastic stroma characteristic to the tumor that contributes to this treatment resistance. Various markers for CAFs have been explored including palladin and CD146 that have prognostic and functional roles in the pathobiology of PDAC. Mechanisms of CAF-tumor cell interaction have been described including exosomal transfer and paracrine signaling mediated by cytokines such as GM-CSF and IL-6. The role of downstream signaling pathways including JAK/STAT, mTOR, sonic hedge hog (SHH), and NFkB have also been shown to play an important function in PDAC-CAF cross talk. The role of autophagy and other metabolic effects on each cell type within the tumor have also been proposed to play roles in facilitating CAF secretory function and enhancing tumor growth in a low-glucose microenvironment. Targeting the stroma has gained interest with multiple preclinical and clinical trials targeting SHH, JAK2, and methods of either exploiting the secretory capability of CAFs to enhance drug delivery or inhibiting it to prevent its influence on cancer cell chemoresistance. This review summarizes the most recent progress made in understanding stromal formation; its contribution to tumor proliferation, invasion, and metastasis; its role in chemoresistance; and potential therapeutic strategies on the horizon.