Järvinen Tero A H, Prince Stuart
School of Medicine, University of Tampere, 33014 Tampere, Finland ; Department of Orthopedics & Traumatology, Tampere University Hospital, 33521 Tampere, Finland.
School of Medicine, University of Tampere, 33014 Tampere, Finland.
Biomed Res Int. 2015;2015:654765. doi: 10.1155/2015/654765. Epub 2015 Nov 30.
Decorin (DCN) is the best characterized member of the extracellular small leucine-rich proteoglycan family present in connective tissues, typically in association with or "decorating" collagen fibrils. It has substantial interest to clinical medicine owing to its antifibrotic, anti-inflammatory, and anticancer effects. Studies on DCN knockout mice have established that a lack of DCN is permissive for tumor development and it is regarded as a tumor suppressor gene. A reduced expression or a total disappearance of DCN has been reported to take place in various forms of human cancers during tumor progression. Furthermore, when used as a therapeutic molecule, DCN has been shown to inhibit tumor progression and metastases in experimental cancer models. DCN affects the biology of various types of cancer by targeting a number of crucial signaling molecules involved in cell growth, survival, metastasis, and angiogenesis. The active sites for the neutralization of different growth factors all reside in different parts of the DCN molecule. An emerging concept that multiple proteases, especially those produced by inflammatory cells, are capable of cleaving DCN suggests that native DCN could be inactivated in a number of pathological inflammatory conditions. In this paper, we review the role of DCN in cancer.
核心蛋白聚糖(DCN)是细胞外富含亮氨酸的小分子蛋白聚糖家族中特征最明确的成员,存在于结缔组织中,通常与胶原纤维结合或“修饰”胶原纤维。由于其抗纤维化、抗炎和抗癌作用,它在临床医学中具有重要意义。对DCN基因敲除小鼠的研究表明,缺乏DCN会促进肿瘤发展,它被视为一种肿瘤抑制基因。据报道,在肿瘤进展过程中,多种人类癌症中都会出现DCN表达降低或完全消失的情况。此外,当用作治疗分子时,DCN已被证明在实验性癌症模型中可抑制肿瘤进展和转移。DCN通过靶向多种参与细胞生长、存活、转移和血管生成的关键信号分子来影响各种类型癌症的生物学行为。中和不同生长因子的活性位点均位于DCN分子的不同部位。一个新出现的概念是,多种蛋白酶,尤其是炎症细胞产生的蛋白酶,能够切割DCN,这表明天然DCN可能在多种病理性炎症条件下失活。在本文中,我们综述了DCN在癌症中的作用。