Department of Pharmacy, University of Salerno, 84084 Fisciano, SA, Italy.
Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", 80131 Naples, NA, Italy.
Int J Mol Sci. 2023 Aug 30;24(17):13427. doi: 10.3390/ijms241713427.
The spread of breast cancer to distant sites is the major cause of death in breast cancer patients. Increasing evidence supports the role of the tumor microenvironment (TME) in breast cancers, and its pathologic assessment has become a diagnostic and therapeutic tool. In the TME, a bidirectional interplay between tumor and stromal cells occurs, both at the primary and metastatic site. Hundreds of molecules, including cytokines, chemokines, and growth factors, contribute to this fine interaction to promote tumor spreading. Here, we investigated the effects of Rimonabant and Cannabidiol, known for their antitumor activity, on reprogramming the breast TME. Both compounds directly affect the activity of several pathways involved in breast cancer progression. To mimic tumor-stroma interactions during breast-to-lung metastasis, we investigated the effect of the compounds on growth factor secretion from metastatic breast cancer cells and normal and activated lung fibroblasts. In this setting, we demonstrated the anti-metastatic potential of the two compounds, and the membrane array analyses highlighted their ability to alter the release of factors involved in the autocrine and paracrine regulation of tumor proliferation, angiogenesis, and immune reprogramming. The results enforce the antitumor potential of Rimonabant and Cannabidiol, providing a novel potential tool for breast cancer TME management.
乳腺癌转移至远处部位是导致乳腺癌患者死亡的主要原因。越来越多的证据支持肿瘤微环境（TME）在乳腺癌中的作用，其病理评估已成为一种诊断和治疗工具。在 TME 中，肿瘤细胞和基质细胞之间存在双向相互作用，无论是在原发部位还是转移部位。包括细胞因子、趋化因子和生长因子在内的数百种分子参与这种精细的相互作用，以促进肿瘤的扩散。在这里，我们研究了雷莫芦单抗和大麻二酚对重塑乳腺 TME 的作用，这两种化合物已知具有抗肿瘤活性。这两种化合物直接影响参与乳腺癌进展的几个途径的活性。为了模拟乳腺到肺转移过程中的肿瘤-基质相互作用，我们研究了化合物对转移性乳腺癌细胞以及正常和激活的肺成纤维细胞生长因子分泌的影响。在这种情况下，我们证明了这两种化合物的抗转移潜力，膜阵列分析强调了它们改变参与肿瘤增殖、血管生成和免疫重编程的自分泌和旁分泌调节的因子释放的能力。这些结果增强了雷莫芦单抗和大麻二酚的抗肿瘤潜力，为乳腺癌 TME 管理提供了一种新的潜在工具。
