Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0149521 (chronic pancreatitis)
 7,199 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is now recognised that epithelial-stromal interactions are important in a wide range of disease processes including neoplasia and inflammation. Metalloproteinases are central to matrix degradation and remodelling, which are key events in tumour invasion and metastasis and may also be involved in tissue changes occurring in chronic inflammation. Immunohistochemistry was performed on sections from 50 patients with pancreatic cancer (n = 27), ampullary cancer (n = 12), low bile duct cancer (n = 3), neuroendocrine tumours (n = 3) and chronic pancreatitis (n = 5), using antibodies raised against collagenase (MMP2), stromelysin (MMP3) and tissue inhibitor of metalloproteinase (TIMP1) and developed using the avidin-biotin complex method. Abundance of MMP2, MMP3 and TIMP1 was greater in pancreatic and ampullary cancer than any other pathology and immunoreactivity in the malignant epithelial cells in pancreatic and ampullary cancer was greater than in the stromal tissues (in pancreatic cancer: MMP2 100% vs 37%, MMP3 93% vs 15%, TIMP1 93% vs 4%, P < 0.0001). There were strong correlations between the immunoreactivity of the two antibodies for MMP2 (P < 0.0001), between MMP2 and TIMP1 (P < 0.0001) and between MMP3 and TIMP1 (P < 0.0001). The immunoreactivity for TIMP1 in pancreatic and ampullary cancers with lymph node metastases was significantly less compared with those cases without lymph node metastases (P < 0.02) and there was an association between increased immunoreactivity for MMP2 and the degree of tumour differentiation (P < 0.01). The results implicate MMP2, MMP3 and TIMP1 in the invasive phenotype of pancreatic and ampullary cancer.
 ...
PMID:Expression of collagenase (MMP2), stromelysin (MMP3) and tissue inhibitor of the metalloproteinases (TIMP1) in pancreatic and ampullary disease. 861 34

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.
 ...
PMID:Expression of extracellular matrix metalloproteinase inducer (EMMPRIN/CD147) in pancreatic neoplasm and pancreatic stellate cells. 1722 48