Madigan Michele C, Kingsley Elizabeth A, Cozzi Paul J, Delprado Warick J, Russell Pamela J, Li Yong
Discipline of Clinical Ophthalmology, Save Sight Institute, University of Sydney, GPO Box 4337, Sydney, NSW 2001, Australia.
Cancer Immunol Immunother. 2008 Sep;57(9):1367-79. doi: 10.1007/s00262-008-0473-x. Epub 2008 Feb 14.
Extracellular matrix metalloproteinase inducer (EMMPRIN/CD147) is a multifunctional membrane glycoprotein overexpressed in many solid tumors, and involved in tumor invasion and angiogenesis. We investigated EMMPRIN expression in human prostate cancer (CaP) tissues and cells, and evaluated whether EMMPRIN expression is related to tumor progression and matrix metalloproteinase (MMPs) expression in human CaP. An immunohistochemical study using tissue microarrays of 120 primary CaPs of different grades and 20 matched lymph node metastases from untreated patients was performed. The association of EMMPRIN expression with clinicopathological parameters was evaluated. Co-immunolocalization for EMMPRIN and MMP-1, MMP-2 or MMP-9 in primary tumors was examined using confocal microscopy. Flow cytometry and immunoblotting were used to examine EMMPRIN expression in 11 metastatic CaP cell lines. Heterogeneous expression of EMMPRIN was found in 78/120 (65%) CaPs, correlated significantly with progression parameters including pre-treatment PSA level (P < 0.05) and increased with progression of CaP (Gleason score, P < 0.05; pathological stage, P < 0.01; nodal involvement, P < 0.05 and surgical margin, P < 0.05). Heterogeneous cytoplasmic MMP-1, MMP-2 and MMP-9 associated with EMMPRIN immunolabeling was observed, particularly in tumors with Gleason scores >3 + 4. Metastatic CaP cell lines, except DuCaP, expressed abundant EMMPRIN protein, indicating highly ( approximately 45 to approximately 65 kDa) and less ( approximately 30 kDa) glycosylated forms, although with no relationship to cells being either androgen responsive or nonresponsive. Our results suggest that EMMPRIN may regulate MMPs and be involved in CaP progression, and as such, could provide a target for treating metastatic CaP disease.
细胞外基质金属蛋白酶诱导剂（EMMPRIN/CD147）是一种多功能膜糖蛋白，在许多实体瘤中过表达，并参与肿瘤侵袭和血管生成。我们研究了EMMPRIN在人前列腺癌（CaP）组织和细胞中的表达，并评估EMMPRIN表达是否与人CaP中的肿瘤进展和基质金属蛋白酶（MMPs）表达相关。对120例不同分级的原发性CaP和20例来自未经治疗患者的匹配淋巴结转移灶进行组织芯片免疫组化研究。评估EMMPRIN表达与临床病理参数的相关性。使用共聚焦显微镜检查原发性肿瘤中EMMPRIN与MMP-1、MMP-2或MMP-9的共免疫定位。采用流式细胞术和免疫印迹法检测11种转移性CaP细胞系中EMMPRIN的表达。在78/120（65%）的CaP中发现EMMPRIN表达异质性，与包括治疗前前列腺特异抗原（PSA）水平在内的进展参数显著相关（P < 0.05），并随CaP进展而增加（Gleason评分，P < 0.05；病理分期，P < 0.01；淋巴结受累，P < 0.05；手术切缘，P < 0.05）。观察到与EMMPRIN免疫标记相关的异质性细胞质MMP-1、MMP-2和MMP-9，特别是在Gleason评分>3 + 4的肿瘤中。除DuCaP外，转移性CaP细胞系表达丰富的EMMPRIN蛋白，显示出高糖基化形式（约45至约65 kDa）和低糖基化形式（约30 kDa），尽管与细胞是否对雄激素有反应无关。我们的结果表明，EMMPRIN可能调节MMPs并参与CaP进展，因此可为治疗转移性CaP疾病提供靶点。
