Expression of extracellular matrix metalloproteinase inducer (EMMPRIN/CD147) in pancreatic neoplasm and pancreatic stellate cells

Abstract

EMMPRIN (extracellular matrix metalloproteinase inducer, CD147) participates in the progression of various malignancies by stimulating the synthesis of specific matrix metalloproteinases (MMP) from peritumoral fibroblasts. In the present study, the expression and functional role of EMMPRIN was investigated in pancreatic neoplasm. QRT-PCR, immunohistochemistry, immunoblot, and ELISA analyses were used to analyze the expression, localization, and release of EMMRPIN. Silencing of EMMPRIN was performed using siRNA oligonucleotides, and functional consequences were assessed using growth assays, invasion assays, as well as MMP1/MMP2 and VEGF ELISA. EMMPRIN mRNA levels were 2.2-fold increased in pancreatic cancer (n = 52) and 2.0-3.5-fold increased in other pancreatic neoplasm (n = 105), but unchanged in chronic pancreatitis (n = 10) compared to normal pancreatic tissues (n = 9). Strong and predominantly membranous immunostaining was observed in the cancer cells and surrounding stromal cells. EMMPRIN serum levels were also significantly increased in pancreatic cancer patients (n = 44) (4.13 ± 0.28 ng/ml) with an AUC of 0.97 compared to healthy volunteers (n = 29) (0.95 ± 0.16 ng/ml; p < 0.0001) and with an AUC of 0.74 compared to chronic pancreatitis patients (n = 20) (2.98 ± 0.5 ng/ml; p = 0.0021). EMMPRIN silencing did not significantly affect anchorage-dependent or -independent growth of pancreatic cancer cells. In contrast, EMMPRIN silencing in pancreatic stellate cells slightly repressed VEGF and MMP2 levels but strongly increased pro-MMP1 expression under coculture conditions. In conclusion, Increased EMMPRIN expression is present in different pancreatic neoplasm, likely representing a tumor-specific reaction with the potential to modulate the tumor microenvironment rather than a mere reflection of an activated stroma.

AZGP1 is a tumor suppressor in pancreatic cancer inducing mesenchymal-to-epithelial transdifferentiation by inhibiting TGF-β-mediated ERK signaling

“…Patients and tissue sampling Tissue sampling and processing was performed as previously described (Zhang et al, 2007). Histological examination was carried out by an experienced pathologist (IE).…”

“…Seven pancreatic cancer cell lines-ASPC1, Capan1, Colo357, MiaPaca2, SU86.86, Panc1 and T3M4-were cultured was previously described (Zhang et al, 2007). PET cell lines were cultured in Dulbecco's modified Eagle's medium (Bon-1 and QGP-1) or RPMI 1640 (CM) cell culture media supplemented with 10% fetal bovine serum, 100 U/ml penicillin and 100 mg/ ml streptomycin at 37 1C, 5% CO 2 .…”

Consensus transcriptome signature of perineural invasion in pancreatic carcinoma

“…Anoikis Assay Cells were plated at a density of 1 × 10 5 per well in 12-well plates coated with 2 mL of a 20 mg/mL polyhydroxyethylmethacrylate/ethanol solution (15). After incubation for 72 h under standard culture conditions, the cell suspension was collected and centrifuged at 1,350 rpm for 10 min and then dissolved in 1:4 diluted binding buffer (1 mL binding buffer and 3 mL distilled water).…”

A role for p53 in the regulation of extracellular matrix metalloproteinase inducer in human cancer cells

“…The roles of EMMPRIN in tumor progression have become increasingly appreciated. For example, it is known that expression of EMMPRIN promotes invasion and metastasis of cancer cells by increasing the production of several matrix metalloproteinases (MMPs) [1][2][3][4][5] and by upregulating the expression vascular endothelial growth factor and angiogenesis. 6 We previously reported that overexpression of EMMPRIN in multidrug resistant cancer cells not only contributes to the enhanced invasive ability, but also to the induction of MDR1 gene whose product is P-glycoprotein, a multidrug transporter.…”