Department of Hematology and Blood Transfusion, School of Allied Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Pathol Res Pract. 2020 May;216(5):152915. doi: 10.1016/j.prp.2020.152915. Epub 2020 Mar 2.
Breast cancer is one of the most important women-related malignancies, which is incurable (particularly in advanced stages) and tumor microenvironment is a number one accused part in the inefficiency of current anti-breast cancer therapeutic strategies. The tumor microenvironment is composed of various cellular and acellular components, which provide an optimum condition for freely expanding cancer cells in various cancer types, particularly breast cancer. Cancer-associated fibroblasts (CAFs) are one of the main cell types in the breast tumor region, which can promote various tumor-promoting processes such as expansion, angiogenesis, metastasis and drug resistance. CAFs directly (by cell-to-cell communication) and indirectly (through secreting soluble factors) can exert their tumorigenic functions. We try to elucidate the immunobiology of CAFs, their origin, function, and heterogeneity in association with their role in various cancer-promoting processes in breast cancer. Based on current knowledge, we believe that the origin of CAFs, their subsets, and their specific expressed biomarkers determine their pro- or anti-tumor functions. Therefore, targeting CAF without considering their specific functions may lead to a deleterious outcome. We propose to find and characterize each subtype of CAFs in association with its specific function in different stages of breast cancer to develop novel promising therapeutic approaches against the right CAF subtype.
乳腺癌是最重要的女性相关恶性肿瘤之一，目前尚无治愈方法（尤其是在晚期），而肿瘤微环境是当前抗乳腺癌治疗策略效率低下的首要原因。肿瘤微环境由各种细胞和非细胞成分组成，为各种癌症类型（尤其是乳腺癌）中癌细胞的自由扩张提供了最佳条件。癌相关成纤维细胞（CAF）是乳腺肿瘤区域的主要细胞类型之一，可促进各种促进肿瘤的过程，如扩张、血管生成、转移和耐药性。CAF 可以直接（通过细胞间通讯）和间接（通过分泌可溶性因子）发挥其致瘤功能。我们试图阐明 CAF 的免疫生物学、它们的起源、功能和异质性，以及它们在乳腺癌中各种促进肿瘤过程中的作用。基于目前的知识，我们认为 CAF 的起源、它们的亚群以及它们特定表达的生物标志物决定了它们的促肿瘤或抗肿瘤功能。因此，不考虑 CAF 的特定功能而靶向 CAF 可能会导致有害的结果。我们建议在不同阶段的乳腺癌中寻找和表征每种 CAF 亚型，并与其特定功能相关联，以开发针对正确 CAF 亚型的有前途的新型治疗方法。
