Tokhanbigli Samaneh, Haghi Mehra, Dua Kamal, Oliver Brian Gregory George
School of Life Science, University of Technology Sydney, Sydney, NSW 2007, Australia.
Respiratory and Cellular Molecular Biology Group, Woolcock Institute of Medical Research, Sydney, NSW 2037, Australia.
Cancer Drug Resist. 2024 Sep 10;7:32. doi: 10.20517/cdr.2024.55. eCollection 2024.
Cancer-associated fibroblasts (CAFs) are the vital constituent of the tumor microenvironment, and in communication with other cells, they contribute to tumor progression and metastasis. Fibroblasts are the proposed origin of CAFs, which are mediated by pro-inflammatory cytokines and the recruitment of immune cells akin to wound healing. Although various studies have identified different subpopulations of CAFs in lung cancer, the heterogeneity of CAFs, particularly in lung cancer, and their potential as a therapeutic target remain largely unknown. Notwithstanding CAFs were previously thought to have predominantly tumor-promoting features, their pro- or anti-tumorigenic properties may depend on various conditions and cell origins. The absence of distinct markers to identify CAF subpopulations presents obstacles to the successful therapeutic targeting and treatment of CAFs in cancer. Human clinical and animal studies targeting CAFs have shown that targeting CAFs exacerbates the disease progression, suggesting that subpopulations of CAFs may exert opposing functions in cancer progression. Therefore, it is essential to pinpoint specific markers capable of characterizing these subpopulations and revealing their mechanisms of function. The cell-specific surface markers of CAFs will serve as an initial step in investigating precise CAF subpopulations and their role in diagnosing and targeting therapy against cancer-promoting CAF subsets in lung cancer.
癌症相关成纤维细胞(CAFs)是肿瘤微环境的重要组成部分,在与其他细胞的相互作用中,它们促进肿瘤进展和转移。成纤维细胞被认为是CAFs的起源,这一过程由促炎细胞因子和类似于伤口愈合的免疫细胞募集介导。尽管各种研究已经在肺癌中鉴定出不同亚群的CAFs,但CAFs的异质性,尤其是在肺癌中的异质性,以及它们作为治疗靶点的潜力在很大程度上仍不清楚。尽管CAFs以前被认为主要具有促进肿瘤的特征,但其促肿瘤或抗肿瘤特性可能取决于各种条件和细胞来源。缺乏识别CAF亚群的独特标志物给成功靶向治疗癌症中的CAFs带来了障碍。针对CAFs的人体临床和动物研究表明,靶向CAFs会加剧疾病进展,这表明CAF亚群在癌症进展中可能发挥相反的作用。因此,确定能够表征这些亚群并揭示其功能机制的特定标志物至关重要。CAFs的细胞特异性表面标志物将作为研究精确的CAF亚群及其在诊断和靶向治疗肺癌中促进癌症的CAF亚群方面作用的第一步。