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.
癌症侵袭是癌症恶性进展（即转移）的必要条件。癌症侵袭机制最初通过体外细胞培养系统进行研究，该系统使用人工细胞外基质（ECMs）培养癌细胞。然而，传统培养系统无法精确模拟体内癌症侵袭过程，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（CAFs）是TME中最丰富的细胞类型，通过促进侵袭、转移、治疗抵抗和免疫抑制来加速癌症进展。因此，CAFs与癌细胞之间的相互作用已被广泛研究，从而发现了介导细胞相互作用的因子，如生长因子、细胞因子和细胞外囊泡。此外，最近研究阐明了癌细胞与CAFs之间直接异型细胞粘附在癌症进展中的重要性。特别是CAFs直接与癌细胞结合，使其能够侵袭ECM并转移至远处器官。本综述总结了CAFs主导的癌症侵袭和转移过程中直接异型细胞相互作用的分子和细胞机制的最新进展，重点关注胃癌。
肿瘤(癌症)患者之家