Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany.
Frankfurt Cancer Institute, Goethe-University Frankfurt, 60596 Frankfurt, Germany.
Int J Mol Sci. 2021 Oct 27;22(21):11636. doi: 10.3390/ijms222111636.
Activationof the tumor-associated stroma to support tumor growth is a common feature observed in different cancer entities. This principle is exemplified by cancer-associated fibroblasts (CAFs), which are educated by the tumor to shape its development across all stages. CAFs can alter the extracellular matrix (ECM) and secrete a variety of different molecules. In that manner they have the capability to affect activation, survival, proliferation, and migration of other stromal cells and cancer cell themselves. Alteration of the ECM, desmoplasia, is a common feature of breast cancer, indicating a prominent role for CAFs in shaping tumor development in the mammary gland. In this review, we summarize the multiple roles CAFs play in mammary carcinoma. We discuss experimental and clinical strategies to interfere with CAFs function in breast cancer. Moreover, we highlight the issues arising from CAFs heterogeneity and the need for further research to identify CAFs subpopulation(s) that can be targeted to improve breast cancer therapy.
肿瘤相关基质的激活以支持肿瘤生长是不同癌症实体中观察到的共同特征。这一原则的例证是癌症相关成纤维细胞(CAFs),它们受到肿瘤的教育,以在所有阶段塑造其发展。CAFs 可以改变细胞外基质(ECM)并分泌各种不同的分子。通过这种方式,它们能够影响其他基质细胞和癌细胞自身的激活、存活、增殖和迁移。ECM 的改变,即纤维变性,是乳腺癌的一个常见特征,表明 CAFs 在塑造乳腺肿瘤发展中起着重要作用。在这篇综述中,我们总结了 CAFs 在乳腺腺癌中发挥的多种作用。我们讨论了干扰 CAFs 在乳腺癌中功能的实验和临床策略。此外,我们强调了 CAFs 异质性所带来的问题,以及需要进一步研究来确定可以靶向以改善乳腺癌治疗的 CAFs 亚群。