胰腺癌中肿瘤相关成纤维细胞的研究进展。
Recent advances in understanding cancer-associated fibroblasts in pancreatic cancer.
机构信息
Hamon Center for Therapeutic Oncology Research, Division of Surgical Oncology, Department of Surgery, Department of Pharmacology, University of Texas Southwestern, Dallas, Texas.
出版信息
Am J Physiol Cell Physiol. 2020 Aug 1;319(2):C233-C243. doi: 10.1152/ajpcell.00079.2020. Epub 2020 May 20.
Pancreatic ductal adenocarcinoma (PDA) is a devastating disease with a poor survival rate. It is resistant to therapy in part due to its unique tumor microenvironment, characterized by a desmoplastic reaction resulting in a dense stroma that constitutes a large fraction of the tumor volume. A major contributor to the desmoplastic reaction are cancer-associated fibroblasts (CAFs). CAFs actively interact with cancer cells and promote tumor progression by different mechanisms, including extracellular matrix deposition, remodeling, and secretion of tumor promoting factors, making CAFs an attractive target for PDA. However, emerging evidences indicate significant tumor-suppressive functions of CAFs, highlighting the complexity of CAF biology. CAFs were once considered as a uniform cell type within the cancer stroma. Recently, the existence of CAF heterogeneity in PDA has become appreciated. Due to advances in single cell technology, distinct subtypes of CAFs have been identified in PDA. Here we review recent updates in CAF biology in PDA, which may help develop effective CAF-targeted therapies in the future.
胰腺导管腺癌 (PDA) 是一种预后极差的毁灭性疾病。它对治疗具有抗性,部分原因是其独特的肿瘤微环境,其特征是促结缔组织反应导致致密基质构成肿瘤体积的很大一部分。促结缔组织反应的一个主要贡献者是癌相关成纤维细胞 (CAF)。CAF 通过不同的机制与癌细胞积极相互作用并促进肿瘤进展,包括细胞外基质的沉积、重塑和肿瘤促进因子的分泌,使 CAF 成为 PDA 的一个有吸引力的治疗靶点。然而,新兴证据表明 CAF 具有显著的肿瘤抑制功能,突出了 CAF 生物学的复杂性。CAF 曾经被认为是癌症基质中一种均匀的细胞类型。最近,人们已经认识到 PDA 中 CAF 的异质性的存在。由于单细胞技术的进步,在 PDA 中已经鉴定出不同的 CAF 亚型。在这里,我们综述了 PDA 中 CAF 生物学的最新进展,这可能有助于未来开发有效的 CAF 靶向治疗。
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