The role of small leucine-rich proteoglycan (SLRP) family in pathological lesions and cancer cell growth
The role of small leucine-rich proteoglycan (SLRP) family in pathological lesions and cancer cell growth
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DOI：
10.1272/jnms.72.137
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发表时间：
2005-06-01
影响因子：
1
通讯作者：
Naito, Zenya
中科院分区：
文献类型：
--
作者：
Naito, Zenya
综述了富含亮氨酸蛋白多糖(SLRP)家族成员LUMICAN在病理性纤维化、肿瘤组织和肿瘤细胞生长中的作用。Lumcan主要集中在病理性纤维化的区域，包括人类冠状动脉内膜增厚、缺血和再灌流的心脏，以及靠近胰腺癌巢的急性胰腺炎和慢性胰腺炎(CP)样病变。在这些病变中，大多数迁移到增厚内膜的血管平滑肌细胞(VSMCs)、缺血灶旁的心肌细胞、病理性胰腺组织的腺泡细胞、胰岛细胞和成纤维细胞都有LUMICA基因和蛋白的瞬时和异位高表达。LUMICA在乳腺癌中的低表达与进展快、生存率低有关。乳腺癌中Lumica mRNA在癌细胞附近的成纤维细胞中过表达，但在癌细胞中不表达。此外，LUMICAN的高表达水平与肿瘤的病理分级高、癌组织中雌激素受体水平低以及患者的年轻有关。抑制LUMICA在培养细胞中的表达可诱导其细胞生长。Lumcan基因转染的肿瘤细胞具有强烈抑制其非锚定生长和侵袭能力的特点。Lumcan可显著抑制同基因小鼠皮下肿瘤的形成，并伴随着细胞周期蛋白D1表达水平的降低，并诱导和/或促进这些细胞的凋亡。肿瘤细胞的自分泌机制以及肿瘤细胞和成纤维细胞通过转化生长因子-β和Smad信号的旁分泌机制可能在SLRPs调节肿瘤生长中发挥重要作用。
The roles of lumican, a member of the small-leucine-rich-proteoglycan (SLRP) family, in pathological fibrosis, cancer tissues and tumor cell growth were reviewed. Lumican is predominantly localized in the areas of pathological fibrosis including the thickened intima of human coronary arteries, ischemic and reperfused hearts, and acute pancreatitis and chronic pancreatitis (CP)-like lesions adjacent to pancreatic cancer nests. In these lesions, lumican mRNA and protein were transiently and ectopically overexpressed in most of the vascular smooth muscle cells (VSMCs) that migrated into the thickened intima, myocardial cells adjacent to an ischemic lesion, acinar cells, islet cells and fibroblasts of pathological pancreatic tissues. The low expression level of lumican in breast cancer is associated with rapid progression and poor survival. Lumican mRNA in breast cancer is overexpressed in fibroblasts adjacent to cancer cells but not in cancer cells. Furthermore, the high expression level of lumican is associated with a high pathological tumor grade, a low estrogen receptor level in the cancer tissues, and young age of patients. The suppression of lumican expression in culture cells induces their cell growth. Lumican-transfected tumor cells are characterized by a strong suppression of their anchorage-independent growth and capacity of invasion. Lumican significantly suppressed subcutaneous tumor formation in syngenic mice, with a concomitant decrease in cyclin D1 expression level, and induced and/or enhanced the apoptosis of these cells. The autocrine mechanism in cancer cells and the paracrine mechanism in cancer cells and fibroblasts via transforming growth factor (TGF)-beta and Smad signals may play important roles in the regulation of tumor growth by SLRPs.