Breast cancer is the most frequently diagnosed cancer in women worldwide. Although dramatically increased survival rates of early diagnosed cases have been observed, late diagnosed patients and metastatic cancer may still be considered fatal. The present study's main focus was on cancer‑associated fibroblasts (CAFs) which is an active component of the tumor microenvironment (TME) regulating the breast cancer ecosystem. Transcriptomic profiling and analysis of CAFs isolated from breast cancer skin metastasis, cutaneous basal cell carcinoma, and squamous cell carcinoma unravelled major gene candidates such as IL6, VEGFA and MFGE8 that induced co‑expression of keratins‑8/‑14 in the EM‑G3 cell line derived from infiltrating ductal breast carcinoma. Western blot analysis of selected keratins (keratin‑8, ‑14, ‑18, ‑19) and epithelial‑mesenchymal transition‑associated markers (SLUG, SNAIL, ZEB1, E‑/N‑cadherin, vimentin) revealed specific responses pointing to certain heterogeneity of the studied CAF populations. Experimental in vitro treatment using neutralizing antibodies against IL-6, VEGF‑A and MFGE8 attenuated the modulatory effect of CAFs on EM‑G3 cells. The present study provided novel data in characterizing and understanding the interactions between CAFs and EM‑G3 cells in vitro. CAFs of different origins support the pro‑inflammatory microenvironment and influence the biology of breast cancer cells. This observation potentially holds significant interest for the development of novel, clinically relevant approaches targeting the TME in breast cancer. Furthermore, its implications extend beyond breast cancer and have the potential to impact a wide range of other cancer types.

中文翻译：

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揭示癌症相关成纤维细胞对乳腺癌 EM-G3 细胞系不良预后标志物的异质性影响：基于转录组分析的体外靶向治疗（抗 IL-6、抗 VEGF-A、抗 MFGE8）。

乳腺癌是全世界女性中最常诊断出的癌症。尽管早期诊断病例的生存率显着提高，但晚期诊断患者和转移性癌症仍可能被认为是致命的。本研究的主要焦点是癌症相关成纤维细胞（CAF），它是调节乳腺癌生态系统的肿瘤微环境（TME）的活性成分。对从乳腺癌皮肤转移、皮肤基底细胞癌和鳞状细胞癌中分离出的 CAF 进行转录组分析，揭示了在 EM-G3 中诱导角蛋白 8/14 共表达的主要候选基因，例如IL6、VEGFA和MFGE8源自浸润性导管乳腺癌的细胞系。对选定角蛋白（角蛋白 8、14、18、19）和上皮间质转化相关标记物（SLUG、SNAIL、ZEB1、E-/N-钙粘蛋白、波形蛋白）进行的蛋白质印迹分析揭示了指向某些特定的特定反应。研究的 CAF 人群的异质性。使用针对 IL-6、VEGF-A 和 MFGE8 的中和抗体进行的体外实验治疗减弱了 CAF 对 EM-G3 细胞的调节作用。本研究为表征和理解 CAF 与 EM-G3 细胞之间的体外相互作用提供了新的数据。不同来源的 CAF 支持促炎微环境并影响乳腺癌细胞的生物学。这一观察结果可能对开发针对乳腺癌 TME 的新型临床相关方法具有重大意义。此外，它的影响超出了乳腺癌范围，并有可能影响广泛的其他癌症类型。