Salehin D, Fromberg I, Haugk C, Dohmen B, Georg T, Bohle R M, Bauerschlag D, Thill M, Friedrich M
Department of Gynecology and Obstretics, Helios Hospital Krefeld, Krefeld, Germany.
Eur J Gynaecol Oncol. 2011;32(6):628-35.
Calpains, also called calcium activated neutral proteases (CANP), are expressed ubiquitously. They are intracellular, non-lysosomal cytoplasmic cysteine endopeptidases. Calcium is required for their activation. Their endogenous specific inhibitor is calpastatin, which is expressed ubiquitously and coexists within cells besides calpain. When calcium is present, calpastatin and calpain attach to each other inhibiting the protease. The calpain system plays an important role in many processes including apoptosis, necrosis, ischemia formation and exocytosis. So far, many reports exist on studies about the influence of calpains in different tumors (skin, breast, renal cell and prostate cancers). The role of calpains in pathogenesis or further tumor progression has always been proved in related studies, but their exact function could not be demonstrated. So far, no studies on calpains being involved in the pathogenesis of ovarian cancer have been published. In our study we focused on the expression of the enzymes calpain 1, calpain 2 and their inhibitor calpastatin in normal and malign ovarian tissue. Therefore, we performed immunohistochemical stainings of paraffin slices and evaluated staining intensity (SI), percentage of positive cells (PP) and immunoreactive score (IRS). We evaluated the correlation between enzyme expression in malign and benign ovarian tissues. In malignant ovarian tissue, we found decreased expression, staining intensity and immunoreactive score of calpastatin. With higher grading of the ovarian carcinoma, staining intensity and immunoreactive score of calpain 1 decreased. Staining intensity of calpain 2 in ovarian carcinoma decreased with increasing lymph node status. We clearly demonstrated differences between enzyme expressions in malign and benign tissue. This study could not find any specific function of calpains. Only few studies in the literature have been found that deal with calpain evaluation of ovarian cancer. Additional studies including more patients are required to elucidate the functional role and impact of calpain in tumors in detail.
钙蛋白酶,也称为钙激活中性蛋白酶(CANP),广泛表达。它们是细胞内的非溶酶体细胞质半胱氨酸内肽酶。其激活需要钙。它们的内源性特异性抑制剂是钙蛋白酶抑制蛋白,该蛋白广泛表达并与钙蛋白酶一起存在于细胞内。当有钙存在时,钙蛋白酶抑制蛋白和钙蛋白酶相互结合,抑制蛋白酶活性。钙蛋白酶系统在包括凋亡、坏死、缺血形成和胞吐作用在内的许多过程中发挥重要作用。到目前为止,有许多关于钙蛋白酶在不同肿瘤(皮肤癌、乳腺癌、肾细胞癌和前列腺癌)中影响的研究报道。在相关研究中,钙蛋白酶在发病机制或肿瘤进一步进展中的作用一直得到证实,但其确切功能尚未得到明确。到目前为止,尚未发表关于钙蛋白酶参与卵巢癌发病机制的研究。在我们的研究中,我们关注钙蛋白酶1、钙蛋白酶2及其抑制剂钙蛋白酶抑制蛋白在正常和恶性卵巢组织中的表达。因此,我们对石蜡切片进行了免疫组织化学染色,并评估了染色强度(SI)、阳性细胞百分比(PP)和免疫反应评分(IRS)。我们评估了恶性和良性卵巢组织中酶表达之间的相关性。在恶性卵巢组织中,我们发现钙蛋白酶抑制蛋白的表达、染色强度和免疫反应评分降低。随着卵巢癌分级的升高,钙蛋白酶1的染色强度和免疫反应评分降低。卵巢癌中钙蛋白酶2的染色强度随着淋巴结状态的增加而降低。我们清楚地证明了恶性和良性组织中酶表达的差异。本研究未发现钙蛋白酶的任何特定功能。在文献中仅发现少数研究涉及卵巢癌的钙蛋白酶评估。需要更多患者参与的进一步研究来详细阐明钙蛋白酶在肿瘤中的功能作用和影响。