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.