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01-09-2008 | Original Article

The role of extracellular matrix metalloproteinase inducer protein in prostate cancer progression

Authors: Michele C. Madigan, Elizabeth A. Kingsley, Paul J. Cozzi, Warick J. Delprado, Pamela J. Russell, Yong Li

Published in: Cancer Immunology, Immunotherapy | Issue 9/2008

Abstract

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 (∼45 to ∼65 kDa) and less (∼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.

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Title: The role of extracellular matrix metalloproteinase inducer protein in prostate cancer progression
Authors: Michele C. Madigan
Elizabeth A. Kingsley
Paul J. Cozzi
Warick J. Delprado
Pamela J. Russell
Yong Li
Publication date: 01-09-2008
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 9/2008
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-008-0473-x

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