Molecular Immunology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Via Venezian, 1, 20133, Milan, Italy.
Cancer Metastasis Rev. 2010 Jun;29(2):295-307. doi: 10.1007/s10555-010-9221-8.
The family of matricellular proteins comprises molecules with disparate biology. The main characteristic of matricellular proteins is to be expressed during tissue renewal and repair in order to "normalize" the tissue. Tumors are wound that do not heal, and tumor growth and metastasis can be viewed as a consequence of aberrant homeostasis, during which matricellular proteins are often upregulated. In the tumor microenvironment, they can be produced by both tumor cells and surrounding stromal cells, such as fibroblasts and macrophages. In this context, matricellular proteins can exert several functions that actively contribute to tumor progression. They may (a) regulate cellular adhesion and migration and extracellular matrix deposition, (b) control tumor infiltration by macrophages or other leukocytes, (c) affect tumor angiogenesis, (d) regulate TGFbeta and other growth factor receptor signals, (e) directly stimulate integrin receptors to transduce pro-survival or pro-migratory signals, and (f) regulate the wnt/beta-catenin pathways. Most of these functions contribute to settle a chronic low inflammatory state, whose involvement in tissue transformation and tumor progression is now established.
细胞外基质蛋白家族包括生物学特性不同的分子。细胞外基质蛋白的主要特征是在组织更新和修复过程中表达，以“使组织正常化”。肿瘤是无法愈合的伤口，肿瘤的生长和转移可以被视为异常动态平衡的结果，在此期间，细胞外基质蛋白通常会被上调。在肿瘤微环境中，它们可以由肿瘤细胞和周围基质细胞（如成纤维细胞和巨噬细胞）产生。在这种情况下，细胞外基质蛋白可以发挥多种积极促进肿瘤进展的功能。它们可以 (a) 调节细胞黏附和迁移以及细胞外基质的沉积，(b) 控制巨噬细胞或其他白细胞浸润肿瘤，(c) 影响肿瘤血管生成，(d) 调节 TGFbeta 和其他生长因子受体信号，(e) 直接刺激整合素受体转导促生存或促迁移信号，以及 (f) 调节 wnt/β-catenin 途径。这些功能大多有助于建立慢性低度炎症状态，其在组织转化和肿瘤进展中的作用现已确立。
