Targeting mast cells tryptase in tumor microenvironment: a potential antiangiogenetic strategy.
Targeting mast cells tryptase in tumor microenvironment: a potential antiangiogenetic strategy.
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DOI：
10.1155/2014/154702
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发表时间：
2014
影响因子：
--
通讯作者：
Ranieri G
中科院分区：
文献类型：
--
作者：
Ammendola M;Leporini C;Marech I;Gadaleta CD;Scognamillo G;Sacco R;Sammarco G;De Sarro G;Russo E;Ranieri G
血管生成是一个复杂的过程，由血管生成刺激剂和抑制剂之间的平衡精细调节。由于促血管生成因子的过度表达，它在癌症的发展中起着至关重要的作用。尽管最初肥大细胞（MC）在超敏反应和免疫中的作用已被定义，但人们发现MC通过释放经典的促血管生成因子（例如，血管内皮生长因子）和颗粒相关的非经典促血管生成介质（主要是类胰蛋白酶）。事实上，在一些动物和人类恶性肿瘤中，MC密度与肿瘤血管生成高度相关。特别是，类胰蛋白酶，蛋白酶激活受体-2（PAR-2）的激动剂，代表了c-Kit受体激活后由人MC释放的最强大的血管生成介质之一。该蛋白酶通过其蛋白水解活性作用于PAR-2，具有血管生成活性，以旁分泌方式刺激人血管内皮细胞和肿瘤细胞增殖，帮助肿瘤细胞侵袭和转移。基于文献数据，它表明类胰蛋白酶可能代表一个有前途的目标，在癌症治疗中，由于其促血管生成活性。在这里，我们集中在三个类胰蛋白酶抑制剂（甲磺酸加贝酯，甲磺酸萘莫司他和曲尼司特）的分子机制，以考虑其在癌症治疗中的前瞻性作用。
Angiogenesis is a complex process finely regulated by the balance between angiogenesis stimulators and inhibitors. As a result of proangiogenic factors overexpression, it plays a crucial role in cancer development. Although initially mast cells (MCs) role has been defined in hypersensitivity reactions and in immunity, it has been discovered that MCs have a crucial interplay on the regulatory function between inflammatory and tumor cells through the release of classical proangiogenic factors (e.g., vascular endothelial growth factor) and nonclassical proangiogenic mediators granule-associated (mainly tryptase). In fact, in several animal and human malignancies, MCs density is highly correlated with tumor angiogenesis. In particular, tryptase, an agonist of the proteinase-activated receptor-2 (PAR-2), represents one of the most powerful angiogenic mediators released by human MCs after c-Kit receptor activation. This protease, acting on PAR-2 by its proteolytic activity, has angiogenic activity stimulating both human vascular endothelial and tumor cell proliferation in paracrine manner, helping tumor cell invasion and metastasis. Based on literature data it is shown that tryptase may represent a promising target in cancer treatment due to its proangiogenic activity. Here we focused on molecular mechanisms of three tryptase inhibitors (gabexate mesylate, nafamostat mesylate, and tranilast) in order to consider their prospective role in cancer therapy.
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