Yamaguchi Hideki, Miyazaki Makoto
Department of Cancer Cell Research, Sasaki Institute, Sasaki Foundation, 2-2 Kandasurugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
Cancers (Basel). 2024 Apr 24;16(9):1636. doi: 10.3390/cancers16091636.
Cancer invasion is a requisite for the most malignant progression of cancer, that is, metastasis. The mechanisms of cancer invasion were originally studied using in vitro cell culture systems, in which cancer cells were cultured using artificial extracellular matrices (ECMs). However, conventional culture systems do not precisely recapitulate in vivo cancer invasion because the phenotypes of cancer cells in tumor tissues are strongly affected by the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are the most abundant cell type in the TME and accelerate cancer progression through invasion, metastasis, therapy resistance, and immune suppression. Thus, the reciprocal interactions between CAFs and cancer cells have been extensively studied, leading to the identification of factors that mediate cellular interactions, such as growth factors, cytokines, and extracellular vesicles. In addition, the importance of direct heterocellular adhesion between cancer cells and CAFs in cancer progression has recently been elucidated. In particular, CAFs are directly associated with cancer cells, allowing them to invade the ECM and metastasize to distant organs. In this review, we summarize the recent progress in understanding the molecular and cellular mechanisms of the direct heterocellular interaction in CAF-led cancer invasion and metastasis, with an emphasis on gastric cancer.
癌症侵袭是癌症最恶性进展即转移的必要条件。癌症侵袭机制最初是使用体外细胞培养系统进行研究的，在该系统中，癌细胞使用人工细胞外基质（ECM）进行培养。然而，传统培养系统不能精确重现体内癌症侵袭情况，因为肿瘤组织中癌细胞的表型受到肿瘤微环境（TME）的强烈影响。癌症相关成纤维细胞（CAF）是TME中最丰富的细胞类型，可通过侵袭、转移、治疗抗性和免疫抑制促进癌症进展。因此，CAF与癌细胞之间的相互作用已得到广泛研究，从而确定了介导细胞间相互作用的因子，如生长因子、细胞因子和细胞外囊泡。此外，最近已阐明癌细胞与CAF之间直接异细胞粘附在癌症进展中的重要性。特别是，CAF与癌细胞直接相关，使其能够侵袭ECM并转移至远处器官。在本综述中，我们总结了在理解CAF介导的癌症侵袭和转移中直接异细胞相互作用的分子和细胞机制方面的最新进展，重点是胃癌。
