ABSTRACT
The carcinogenesis and progression of cancer not only depend on the feature of tumor cell themselves, but also rely on the tumor microenvironment (TME). Numerous studies have shown that TME plays a crucial role in tumor progression and drug resistance. Cancer-associated fibroblasts (CAFs) are important stromal cells in TME containing multiple functions, such as remodeling the extracellular matrix, regulating angiogenesis, interacting with adjacent tumor cells, and releasing a variety of molecules (such as cytokines, growth factors and exosomes) to regulate cell proliferation, invasion and metastasis. CAFs exhibit heterogeneity of origin and phenotype, and play dual roles in tumor progression. Recent studies have shown that CAFs are also involved in chemoresistance, suggesting that CAFs themselves and their downstream molecules and signal pathways could be the potential therapeutic target for cancer treatment. In this review, we summarized the role of CAFs in chemoresistance and underlying mechanism, and discussed the potential of targeting CAFs in overcoming drug resistance. However, the exploration of strategy for targeting CAFs is still at an early stage and requires further in-depth research.
ABSTRACT
Cancer-associated fibroblasts(CAFs) are important cellular components of the tumor microenvironment. They have a variety of cellular sources, including resident fibroblasts, bone marrow mesenchymal stem cells and epithelial cells, which contribute to the development of tumors. CAFs play important roles in cancer initiation, progression, and metastasis,which can promote tumor proliferation and migration, promote tumor angiogenesis, regulate tumor immunity, and improve tumor drug resistance. Therefore, it is a promising development direction in tumor-targeted therapy. CAFs regulate the biological characteristics of tumor cells and other stromal cells through cell-to-cell contact, releases many regulatory factors and synthesizes and reshapes the extracellular matrix, and influences the occurrence and development of cancer in these ways. However, there are still many unresolved issues on the way in targeting CAFs for tumor therapy. For example, the origin and functional heterogeneity of CAFs still need to be further explored. This review mainly focuses on the summary of origin of CAFs, their roles in tumor development and the potential application in cancer targeted therapy, which will help to deepen the understanding of the roles of CAFs in cancer development and future cancer treatment.
ABSTRACT
Cancer-associated fibroblasts (CAFs) are a major population that resides in the tumor microenvironment. Multiple soluble molecules secreted by CAFs remodel the extracellular matrix, thus promoting tumor growth, invasion and metastasis. It is now considered that CAFs play an important role in the regulation of tumor immunity, in which an increasing number of molecular mechanisms of tumor microenvironment remodeling are being discovered. This article reviews the molecular markers of CAFs, the crosstalk between CAFs and tumor cells or immune cells, as well as the progress on therapeutic targeting of CAFs.
ABSTRACT
@#[Abstract] Cancer-associated fibroblasts (CAFs) are one of the most abundant and critical components in tumor microenvironment, which not only provide physical support for tumor cells, but also play a key role in promoting or delaying tumor occurrence and development. CAFs are a highly abundant and heterogeneous mesenchymal cell line, which contain a large number of cell subsets with different phenotypes and functions. Targeted therapies for CAFs also emerge as demanded. In order to improve the understanding of CAFs in malignant tumors, we elucidate the heterogeneity of CAFs origins, phenotypes and related functions, as well as the research progress of their application in targeted therapy.