Fedele Monica, Cerchia Laura, Chiappetta Gennaro
CNR-Institute of Experimental Endocrinology and Oncology, 80131 Naples, Italy.
Dipartimento di Ricerca Traslazionale a Supporto dei Percorsi Oncologici, S.C. Genomica Funzionale, Istituto Nazionale Tumori-IRCCS-Fondazione G Pascale, 80131 Naples, Italy.
Cancers (Basel). 2017 Sep 30;9(10):134. doi: 10.3390/cancers9100134.
Breast cancer is a heterogeneous disease that is characterized by a high grade of cell plasticity arising from the contribution of a diverse range of factors. When combined, these factors allow a cancer cell to transition from an epithelial to a mesenchymal state through a process of dedifferentiation that confers stem-like features, including chemoresistance, as well as the capacity to migrate and invade. Understanding the complex events that lead to the acquisition of a mesenchymal phenotype will therefore help to design new therapies against metastatic breast cancer. Here, we recapitulate the main endogenous molecular signals involved in this process, and their cross-talk with paracrine factors. These signals and cross-talk include the extracellular matrix; the secretome of cancer-associated fibroblasts, macrophages, cancer stem cells, and cancer cells; and exosomes with their cargo of miRNAs. Finally, we highlight some of the more promising therapeutic perspectives based on counteracting the epithelial-to-mesenchymal transition in breast cancer cells.
乳腺癌是一种异质性疾病,其特征是由于多种因素的作用而具有高度的细胞可塑性。这些因素共同作用,使癌细胞通过去分化过程从上皮状态转变为间充质状态,从而赋予其干细胞样特征,包括化疗耐药性以及迁移和侵袭能力。因此,了解导致间充质表型获得的复杂事件将有助于设计针对转移性乳腺癌的新疗法。在这里,我们概述了该过程中涉及的主要内源性分子信号,以及它们与旁分泌因子的相互作用。这些信号和相互作用包括细胞外基质;癌症相关成纤维细胞、巨噬细胞、癌症干细胞和癌细胞的分泌组;以及携带miRNA的外泌体。最后,我们强调了一些基于对抗乳腺癌细胞上皮-间充质转化的更有前景的治疗前景。