Tumors are characterized by extracellular matrix (ECM) deposition, remodeling, and cross-linking that drive fibrosis to stiffen the stroma and promote malignancy. The stiffened stroma enhances tumor cell growth, survival and migration and drives a mesenchymal transition. A stiff ECM also induces angiogenesis, hypoxia and compromises anti-tumor immunity. Not surprisingly, tumor aggression and poor patient prognosis correlate with degree of tissue fibrosis and level of stromal stiffness. In this review, we discuss the reciprocal interplay between tumor cells, cancer associated fibroblasts (CAF), immune cells and ECM stiffness in malignant transformation and cancer aggression. We discuss CAF heterogeneity and describe its impact on tumor development and aggression focusing on the role of CAFs in engineering the fibrotic tumor stroma and tuning tumor cell tension and modulating the immune response. To illustrate the role of mechanoreciprocity in tumor evolution we summarize data from breast cancer and pancreatic ductal carcinoma (PDAC) studies, and finish by discussing emerging anti-fibrotic strategies aimed at treating cancer.

中文翻译：

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纤维化和癌症：一种紧张的关系。

肿瘤的特点是细胞外基质 (ECM) 沉积、重塑和交联，它们驱动纤维化以使基质变硬并促进恶性肿瘤。硬化的基质增强了肿瘤细胞的生长、存活和迁移，并推动了间充质转化。僵硬的 ECM 还会诱导血管生成、缺氧并损害抗肿瘤免疫。毫不奇怪，肿瘤侵袭性和患者预后不良与组织纤维化程度和基质硬度水平相关。在这篇综述中，我们讨论了肿瘤细胞、癌症相关成纤维细胞 (CAF)、免疫细胞和 ECM 硬度在恶性转化和癌症侵袭中的相互作用。我们讨论 CAF 异质性并描述其对肿瘤发展和侵袭的影响，重点关注 CAF 在工程纤维化肿瘤基质和调节肿瘤细胞张力和调节免疫反应中的作用。为了说明机械互易性在肿瘤进化中的作用，我们总结了来自乳腺癌和胰腺导管癌 (PDAC) 研究的数据，最后讨论了旨在治疗癌症的新兴抗纤维化策略。