Matarrese Paola, Mattia Gianfranco, Pagano Maria Teresa, Pontecorvi Giada, Ortona Elena, Malorni Walter, Carè Alessandra
Center for Gender Specific Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy.
Department of Biology, Faculty of Farmacy, University of Rome Tor Vergata, 00133 Rome, Italy.
Cancers (Basel). 2021 Jun 30;13(13):3287. doi: 10.3390/cancers13133287.
The interplay between cancer cells and the tumor microenvironment (TME) has a fundamental role in tumor progression and response to therapy. The plethora of components constituting the TME, such as stroma, fibroblasts, endothelial and immune cells, as well as macromolecules, e.g., hormones and cytokines, and epigenetic factors, such as microRNAs, can modulate the survival or death of cancer cells. Actually, the TME can stimulate the genetically regulated programs that the cell puts in place under stress: apoptosis or, of interest here, autophagy. However, the implication of autophagy in tumor growth appears still undefined. Autophagy mainly represents a cyto-protective mechanism that allows cell survival but, in certain circumstances, also leads to the blocking of cell cycle progression, possibly leading to cell death. Since significant sex/gender differences in the incidence, progression and response to cancer therapy have been widely described in the literature, in this review, we analyzed the roles played by key components of the TME, e.g., estrogen and microRNAs, on autophagy regulation from a sex/gender-based perspective. We focused our attention on four paradigmatic and different forms of cancers-colon cancer, melanoma, lymphoma, and lung cancer-concluding that sex-specific differences may exert a significant impact on TME/cancer interaction and, thus, tumor growth.
癌细胞与肿瘤微环境（TME）之间的相互作用在肿瘤进展和对治疗的反应中起着至关重要的作用。构成TME的大量成分，如基质、成纤维细胞、内皮细胞和免疫细胞，以及大分子，如激素和细胞因子，还有表观遗传因子，如微小RNA，都可以调节癌细胞的存活或死亡。实际上，TME可以刺激细胞在应激状态下启动的基因调控程序：凋亡，或者在这里值得关注的自噬。然而，自噬在肿瘤生长中的作用似乎仍不明确。自噬主要代表一种细胞保护机制，它能使细胞存活，但在某些情况下，也会导致细胞周期进程受阻，可能导致细胞死亡。由于文献中已广泛描述了癌症发病率、进展和对癌症治疗反应方面显著的性别差异，在本综述中，我们从性别角度分析了TME的关键成分，如雌激素和微小RNA，在自噬调节中所起的作用。我们将注意力集中在四种典型且不同类型的癌症——结肠癌、黑色素瘤、淋巴瘤和肺癌上，得出结论：性别特异性差异可能对TME/癌症相互作用以及肿瘤生长产生重大影响。
