Lionetti Maria Chiara, Cola Filippo, Chepizhko Oleksandr, Fumagalli Maria Rita, Font-Clos Francesc, Ravasio Roberto, Minucci Saverio, Canzano Paola, Camera Marina, Tiana Guido, Zapperi Stefano, Porta Caterina A M La
Center for Complexity and Biosystems, Department of Environmental Science and Policy, University of Milan, via Celoria 26, 20133 Milano, Italy.
Center for Complexity and Biosystems, Department of Physics, University of Milan, via Celoria 16, 20133 Milano, Italy.
J Clin Med. 2020 Aug 8;9(8):2573. doi: 10.3390/jcm9082573.
Melanoma is one of the most aggressive and highly resistant tumors. Cell plasticity in melanoma is one of the main culprits behind its metastatic capabilities. The detailed molecular mechanisms controlling melanoma plasticity are still not completely understood. Here we combine mathematical models of phenotypic switching with experiments on IgR39 human melanoma cells to identify possible key targets to impair phenotypic switching. Our mathematical model shows that a cancer stem cell subpopulation within the tumor prevents phenotypic switching of the other cancer cells. Experiments reveal that hsa-mir-222 is a key factor enabling this process. Our results shed new light on melanoma plasticity, providing a potential target and guidance for therapeutic studies.
黑色素瘤是最具侵袭性和高抗性的肿瘤之一。黑色素瘤中的细胞可塑性是其转移能力背后的主要罪魁祸首之一。控制黑色素瘤可塑性的详细分子机制仍未完全了解。在这里，我们将表型转换的数学模型与对IgR39人黑色素瘤细胞的实验相结合，以确定可能损害表型转换的关键靶点。我们的数学模型表明，肿瘤内的癌症干细胞亚群可阻止其他癌细胞的表型转换。实验表明，hsa-mir-222是促成这一过程的关键因素。我们的结果为黑色素瘤可塑性提供了新的线索，为治疗研究提供了潜在的靶点和指导。
