Seprase, a membrane-bound protease, is overexpressed by invasive ductal carcinoma cells of human breast cancers.
Seprase, a membrane-bound protease, is overexpressed by invasive ductal carcinoma cells of human breast cancers.
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发表时间：
1998-09
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通讯作者：
Thomas Kelly;S. Kechelava;Tricia L. Rozypal;West Kw;S. Korourian
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作者：
Thomas Kelly;S. Kechelava;Tricia L. Rozypal;West Kw;S. Korourian
丝氨酸整合膜蛋白酶seprase的细胞表面表达增加与体外人黑色素瘤细胞系的侵袭行为相关。本研究调查了seprase在恶性、癌前、良性和正常人乳腺组织中的表达。在浸润性导管癌（IDC）的提取物中鉴定了Seprase的170-kDa明胶酶活性。对应于具有蛋白水解活性的170-kDa seprase二聚体及其97-kDa seprase亚基蛋白的蛋白条带通过使用针对免疫亲和纯化的seprase引起的抗血清对IDC提取物进行免疫印迹分析来鉴定。41例经福尔马林固定和石蜡包埋的人乳腺组织中seprase表达的免疫组化分析显示，27例与IDC的恶性细胞优先免疫反应。在个别IDC标本，间质细胞或形态正常的上皮细胞显示低标记，总是显着低于标记的肿瘤细胞。IDC细胞的淋巴结转移也呈强阳性，但受累淋巴结的淋巴组织不染色。原位DC中的肿瘤细胞（5例）表现出不同程度的染色。良性纤维腺瘤（2例）和良性增生性乳腺疾病（5例）的上皮细胞呈弱阳性或阴性。正常乳腺组织（1例）上皮细胞未染色。DC细胞对seprase的过表达与seprase在促进乳腺IDC的侵袭和转移中的作用一致。Seprase的细胞表面定位可用于将治疗剂靶向至恶性乳腺细胞。
The increased cell surface expression of the serine integral membrane protease, seprase, has been associated with the invasive behavior of human melanoma cell lines in vitro. The present study investigates the expression of seprase in malignant, premalignant, benign, and normal human breast tissues. The 170-kDa gelatinase activity of seprase was identified in extracts of infiltrating ductal carcinomas (IDC). Protein bands corresponding to the proteolytically active 170-kDa seprase dimer and its 97-kDa seprase subunit protein were identified by immunoblot analysis of IDC extracts using an antiserum elicited against immunoaffinity-purified seprase. Immunohistochemical analysis of seprase expression in 41 formalin-fixed and paraffin-embedded specimens of human breast tissue revealed preferential immunoreactivity with the malignant cells of IDC (27 cases). Within individual IDC specimens, the stromal cells or morphologically normal epithelium revealed low labeling that was always significantly less than the labeling of neoplastic cells. Lymph node metastases of IDC cells were also strongly positive, but the lymphoid tissue in affected nodes was not stained. Neoplastic cells in DC in situ (5 cases) exhibited variable levels of staining. Epithelial cells of benign fibroadenoma specimens (2 cases) and benign proliferative breast disease (5 cases) exhibited little or no immunoreactivity. Epithelial cells of normal breast tissue (1 case) were not stained. The overexpression of seprase by DC cells is consistent with seprase having a role in facilitating invasion and metastasis of IDC of the breast. The cell surface localization of seprase could be used to target therapeutic agents to malignant breast cells.