Nutrition, Growth and Cancer, Université François-Rabelais de Tours, Inserm U, France.
Eur J Cell Biol. 2012 Nov-Dec;91(11-12):847-60. doi: 10.1016/j.ejcb.2012.04.004. Epub 2012 Jun 4.
Invadosomes are actin-rich finger-like cellular structures sensing and interacting with the surrounding extracellular matrix (ECM) and involved in its proteolytic remodeling. Invadosomes are structures distinct from other adhesion complexes, and have been identified in normal cells that have to cross tissue barriers to fulfill their function such as leukocytes, osteoclasts and endothelial cells. They also represent features of highly aggressive cancer cells, allowing them to escape from the primary tumor, to invade surrounding tissues and to reach systemic circulation. They are localized to the ventral membrane of cells grown under 2-dimensional conditions and are supposed to be present all around cells grown in 3-dimensional matrices. Indeed invadosomes are key structures in physiological processes such as inflammation and the immune response, bone remodeling, tissue repair, but also in pathological conditions such as osteopetrosis and the development of metastases. Invadosomes are subdivided into podosomes, found in normal cells, and into invadopodia specific for cancer cells. While these two structures exhibit differences in organization, size, number and half-life, they share similarities in molecular composition, participation in cell-matrix adhesion and promoting matrix degradation. A key determinant in invadosomal function is the recruitment and release of proteases, such as matrix metalloproteinases (MMPs), serine proteases and cysteine cathepsins, together with their activation in a tightly controlled and highly acidic microenvironment. Therefore numerous pH regulators such as V-ATPases and Na(+)/H(+) exchangers, are found in invadosomes and are directly involved in their constitution as well as their functioning. This review focuses on the participation of pH regulators in invadosome function in physiological and pathological conditions, with a particular emphasis on ECM remodeling by osteoclasts during bone resorption and by cancer cells.
侵袭小体是富含肌动蛋白的指状细胞结构，可感应和相互作用于周围细胞外基质（ECM），并参与其蛋白水解重塑。侵袭小体与其他黏附复合物不同，在需要穿过组织屏障以发挥功能的正常细胞中已被识别，如白细胞、破骨细胞和内皮细胞。它们也是高度侵袭性癌细胞的特征，使它们能够从原发性肿瘤中逃脱，侵袭周围组织并到达全身循环。它们定位于在二维条件下生长的细胞的腹膜上，并且应该存在于在三维基质中生长的所有细胞周围。实际上，侵袭小体是生理过程中的关键结构，如炎症和免疫反应、骨重塑、组织修复，但也存在于病理条件下，如骨质疏松症和转移的发展。侵袭小体分为破骨细胞中的破骨小体和癌细胞特有的侵袭小体。虽然这两种结构在组织、大小、数量和半衰期上存在差异，但它们在分子组成、参与细胞基质黏附和促进基质降解方面具有相似性。侵袭小体功能的关键决定因素是蛋白酶的募集和释放，如基质金属蛋白酶（MMPs）、丝氨酸蛋白酶和半胱氨酸组织蛋白酶，以及它们在严格控制的高度酸性微环境中的激活。因此，许多 pH 调节剂，如 V-ATPases 和 Na(+)/H(+) 交换器，存在于侵袭小体中，并直接参与其组成及其功能。这篇综述重点介绍了 pH 调节剂在生理和病理条件下侵袭小体功能中的参与，特别是破骨细胞在骨吸收过程中以及癌细胞在 ECM 重塑中的参与。
