The analysis of the role and inhibition of heparanase in cancer metastasis and inflammation

乙酰肝素酶(heparanase，HPA)是一种内切硫酸乙酰肝素蛋白多糖(HSPG)糖链的内切酶，广泛存在于细胞表面和细胞外基质(包括基底膜)中。HSPGs还结合和隔离各种生物活性蛋白，包括生长因子、趋化因子、细胞因子和酶。HPA切割HSPGs后，释放并激活与HS结合的生长因子，如bFGF、TGF-b、PDGF和VEGF。HPA参与胚胎形态发生、伤口愈合、组织修复和炎症反应。该酶已在各种正常和恶性细胞和组织中发现，如皮肤成纤维细胞、细胞滋养细胞、肝细胞、内皮细胞、血小板、肥大细胞、中性粒细胞、巨噬细胞、T和B淋巴细胞、淋巴瘤、黑色素瘤和癌细胞。以往的研究表明，hpa基因和蛋白的表达与几种人和小鼠…的转移潜能有关。更多的细胞系，如乳腺癌、膀胱癌、前列腺癌、黑色素瘤和T淋巴瘤。我们发现乙酰肝素酶在胃癌的侵袭和转移以及其他肿瘤中起着重要的作用。(Uno F，Naomoto Y等人；反义介导的抑制人乙酰肝素酶基因表达抑制人类癌细胞的胸膜扩散。癌症研究61(21)：7855-60,2001，Takaoka M，Naomoto Y等人；乙酰肝素酶的表达与胃癌的侵袭和不良预后相关。实验室投资。83(5)：613-22,2003)肝素酶在炎症性肠病和其他疾病中也起着重要作用。这些结果发表在以下期刊上；(Nobuhisa T，Naomoto Y等人；肝素酶是结肠癌预后不良和恶性潜能的标志。在临床癌症研究/Imada T上提交，Naomoto Y等人；环氧合酶-2-乙酰肝素酶诱导乳腺癌进展。提交于癌症研究/Ohkawa T，Naomoto Y等人；食道癌细胞中乙酰肝素酶的细胞质和核定位：在预后和分化中分别扮演的角色。发表在癌症研究杂志上)更少

Heparanase (Hpa) is an endo-b-D-glucuronidase that specifically cleaves carbohydrate chains of heparan sulfate proteoglycans (HSPG) s. HSPGs are distributed ubiquitously and are common constituents of cell surfaces and the ECM, including basement membranes. HSPGs also bind and sequester a variety of bioactive proteins, including growth factors, chemokines, cytokines, and enzymes. After cleaving HSPGs by Hpa, HS-binding growth factors, such as bFGF, TGF-b, PDGF and VEGF, are released and activated. Hpa is involved in embryonic morphogenesis, wound healing, tissue repair and inflammation. The enzyme has been identified in a variety of normal and malignant cells and tissues, e.g., skin fibroblasts, cytotrophoblasts, hepatocytes, endothelial cells, platelets, mast cells, neutrophils, macrophages, T and B-lymphocytes, lymphoma, melanoma, and cancer cells. Previous studies demonstrated that the expression of Hpa gene and protein correlated with metastatic potential of several human and mouse … More cell lines such as breast, bladder, prostate, melanoma and T-lymphoma. We found that heparanase had an important role in gastric cancer invasion and metastasis and in other tumors. (Uno F, Naomoto Y et al; Antisense-mediated suppression of human heparanase gene expression inhibits pleural dissemination of human cancer cells. Cancer Res. 61(21):7855-60, 2001, Takaoka M, Naomoto Y et al; Heparanase expression correlates with invasion and poor prognosis in gastric cancers. Lab Invest. 83(5):613-22, 2003 )Heparanase has also important roles in inflammatory bowel disease and other diseases. Those results were submitted in the journals as follows ; (Nobuhisa T, Naomoto Y et al; Heparanase is a marker of poor prognosis and malignant potential of colon cancer. Submitted, in Clinical Cancer Research / Imada T, Naomoto Y et al; COX-2-induction by heparanase in the progession of breast cancer. Submitted in Cancer Research / Ohkawa T, Naomoto Y et al; Cytoplasmic, and nuclear localization of heparanase in esophageal cancer cells : Respective roles in prognosis and differentiation. Submitted in Cancer Research) Less