Nisticò Paola, Di Modugno Francesca, Spada Sheila, Bissell Mina J
Laboratory of Immunology, Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome, 00144, Italy.
Breast Cancer Res. 2014;16(5):459. doi: 10.1186/s13058-014-0459-x.
Following a highly dynamic and complex dialogue between the epithelium and the surrounding microenvironment, the mammary gland develops into a branching structure during puberty, buds during pregnancy, forms intricate polar acini during lactation and, once the babies are weaned, remodels and involutes. At every stage of menstrual and pregnancy cycles, interactions between the cells and the extracellular matrix (ECM) and homotypic and heterotypic cell–cell interactions give rise to the architecture and function of the gland at that junction. These orchestrated programs would not be possible without the important role of the ECM receptors, integrins being the prime examples. The ECM–integrin axis regulates many crucial cellular functions including survival, migration and quiescence; the imbalance in any of these processes could contribute to oncogenesis. In this review we spotlight the involvement of two prominent integrin subunits, β1 and β4 integrins, in cross-talk with tyrosine kinase receptors, and we discuss the roles of these integrin subunits in the biology of normal breast differentiation and as potential prognostic and therapeutic targets in breast cancer.
在乳腺上皮细胞与周围微环境进行高度动态且复杂的对话之后，乳腺在青春期发育成分支结构，在孕期形成芽体，在哺乳期形成错综复杂的极性腺泡，而在婴儿断奶后，乳腺则会重塑并退化。在月经周期和妊娠周期的每个阶段，细胞与细胞外基质（ECM）之间的相互作用以及同型和异型细胞间的相互作用，决定了该阶段乳腺的结构和功能。如果没有ECM受体（整合素是主要例子）的重要作用，这些精心编排的程序将无法实现。ECM-整合素轴调节许多关键的细胞功能，包括存活、迁移和静止；这些过程中任何一个的失衡都可能导致肿瘤发生。在这篇综述中，我们重点介绍了两种突出的整合素亚基β1和β4整合素与酪氨酸激酶受体相互作用的情况，并讨论了这些整合素亚基在正常乳腺分化生物学中的作用，以及它们作为乳腺癌潜在预后和治疗靶点的作用。
