食管癌中癌症相关成纤维细胞与细胞外基质之间的相互作用

Interactions between cancer-associated fibroblasts and the extracellular matrix in oesophageal cancer.

作者信息

Vadibeler Subashan, Clarke Shannique, Phyu Su M, Parkes Eileen E

机构信息

Centre for Immuno-Oncology, Nuffield Department of Medicine, University of Oxford, United Kingdom; Department of Oncology, University of Oxford, United Kingdom.

Department of Oncology, University of Oxford, United Kingdom.

出版信息

Matrix Biol. 2025 Aug;139:49-60. doi: 10.1016/j.matbio.2025.05.003. Epub 2025 May 14.

Abstract

Stromal components of the tumour microenvironment, such as cancer-associated fibroblasts (CAFs) and the extracellular matrix (ECM), are actively involved in tumorigenesis. CAFs and the ECM co-evolve with resultant molecular and mechanical pressure on tumour cells mediated by CAFs via the ECM. Meanwhile, ECM fibers determine CAF differentiation and activity, establishing a protumorigenic feed-forward loop. Oesophageal cancer carries a high morbidity and mortality, and curative surgical resection is only an option for a limited number of patients while early lymphatic spread and poor therapeutic responses are common. Although studies report marked heterogeneity in investigation of the stromal density of gastrointestinal cancers, it is generally accepted that oesophageal cancer is highly fibrotic, and stromal components like CAFs may outnumber cancer cells. Therefore, a comprehensive understanding of the reciprocal interaction between CAFs and the ECM in oesophageal cancer is essential to improving diagnostics and prognostication, as well as designing innovative anti-cancer strategies. Here, we summarise current understanding of oesophageal cancer from a stromal perspective. Then, we discuss that CAFs and the ECM in oesophageal cancer can independently and synergistically contribute to tumour progression and therapeutic resistance. We also summarise potential stromal targets that have been described in transcriptomic analyses, highlighting those validated in downstream experimental studies. Importantly, clinical translation of stromal-targeting strategies in oesophageal cancer is still in its infancy but holds significant promise for future therapeutic combinations.

摘要

肿瘤微环境的基质成分,如癌症相关成纤维细胞(CAFs)和细胞外基质(ECM),积极参与肿瘤发生。CAFs和ECM共同进化,通过ECM对肿瘤细胞产生分子和机械压力。同时,ECM纤维决定CAF的分化和活性,形成一个促肿瘤的前馈回路。食管癌发病率和死亡率高,根治性手术切除仅适用于少数患者,早期淋巴转移和治疗反应差很常见。尽管研究报告在胃肠道癌基质密度研究中存在显著异质性,但一般认为食管癌高度纤维化,像CAFs这样的基质成分可能比癌细胞数量更多。因此,全面了解食管癌中CAFs与ECM之间的相互作用对于改善诊断和预后以及设计创新的抗癌策略至关重要。在此,我们从基质角度总结目前对食管癌的认识。然后,我们讨论食管癌中的CAFs和ECM可独立和协同促进肿瘤进展及治疗耐药性。我们还总结了转录组分析中描述的潜在基质靶点,突出那些在下游实验研究中得到验证的靶点。重要的是,食管癌基质靶向策略的临床转化仍处于起步阶段,但对未来治疗联合具有重大前景。

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