Cancer-Associated Fibroblasts: Heterogeneity and Bimodality in Oncogenesis

Abstract

Malignant tumors are characterized by high cellular heterogeneity, including cancerous and non-malignant cells, as well as non-cellular components that are part of the tumor microenvironment. Cancer-associated fibroblasts often form a major component of the microenvironment, providing the very “soil” in which cancer cells thrive. Cancer-associated fibroblasts may contribute to tumor growth, invasion, metastasis, and resistance to therapy. However, clinical trials of treatment strategies targeting cancer-associated fibroblasts have largely failed. Moreover, there is evidence that cancer-associated fibroblasts are able to inhibit tumor development. In this review, we aimed to present the current understanding of the functional heterogeneity of cancer-associated fibroblasts, their bimodality in tumor development, and tumor progression. Understanding the tumor-promoting and tumor-inhibiting activities of cancer-associated fibroblasts may contribute to the development of new diagnostic and therapeutic approaches.