Department of Cell Pathology, Faculty of Biotechnology, University of Wroclaw, Joliot-Curie 14a, 50-383 Wroclaw, Poland.
Department of Oncology and Division of Surgical Oncology, Wroclaw Medical University, Plac Hirszfelda 12, 53-413 Wroclaw, Poland.
Int J Mol Sci. 2021 Jan 7;22(2):529. doi: 10.3390/ijms22020529.
Malignant melanoma is a highly metastatic type of cancer, which arises frequently from transformed pigment cells and melanocytes as a result of long-term UV radiation exposure. In recent years, the incidence of newly diagnosed melanoma patients reached 5% of all cancer cases. Despite the development of novel targeted therapies directed against melanoma-specific markers, patients' response to treatment is often weak or short-term due to a rapid acquisition of drug resistance. Among the factors affecting therapy effectiveness, elements of the tumor microenvironment play a major role. Melanoma niche encompasses adjacent cells, such as keratinocytes, cancer-associated fibroblasts (CAFs), adipocytes, and immune cells, as well as components of the extracellular matrix and tumor-specific physicochemical properties. In this review, we summarize the current knowledge concerning the influence of cancer-associated cells (keratinocytes, CAFs, adipocytes) on the process of melanomagenesis, tumor progression, invasiveness, and the emergence of drug resistance in melanoma. We also address how melanoma can alter the differentiation and activation status of cells present in the tumor microenvironment. Understanding these complex interactions between malignant and cancer-associated cells could improve the development of effective antitumor therapeutic strategies.
恶性黑色素瘤是一种高度转移性癌症，主要由长期紫外线辐射暴露导致的色素细胞和黑素细胞转化而来。近年来，新诊断的黑色素瘤患者的发病率达到所有癌症病例的 5%。尽管针对黑色素瘤特异性标志物的新型靶向治疗方法不断发展，但由于药物耐药性的迅速获得，患者对治疗的反应往往较弱或短暂。在影响治疗效果的因素中，肿瘤微环境的因素起着重要作用。黑色素瘤生态位包含相邻细胞，如角质形成细胞、癌相关成纤维细胞（CAFs）、脂肪细胞和免疫细胞，以及细胞外基质成分和肿瘤特异性理化特性。在这篇综述中，我们总结了目前关于癌相关细胞（角质形成细胞、CAFs、脂肪细胞）对黑色素瘤发生、肿瘤进展、侵袭性和耐药性出现过程的影响的知识。我们还讨论了黑色素瘤如何改变肿瘤微环境中存在的细胞的分化和激活状态。了解这些恶性和癌相关细胞之间的复杂相互作用可能有助于开发有效的抗肿瘤治疗策略。
