Pathobiological Implications of MUC16 Expression in Pancreatic Cancer

Abstract

MUC16 (CA125) belongs to a family of high-molecular weight O-glycosylated proteins known as mucins. While MUC16 is well known as a biomarker in ovarian cancer, its expression pattern in pancreatic cancer (PC), the fourth leading cause of cancer related deaths in the United States, remains unknown. The aim of our study was to analyze the expression of MUC16 during the initiation, progression and metastasis of PC for possible implication in PC diagnosis, prognosis and therapy. In this study, a microarray containing tissues from healthy and PC patients was used to investigate the differential protein expression of MUC16 in PC. MUC16 mRNA levels were also measured by RT-PCR in the normal human pancreatic, pancreatitis, and PC tissues. To investigate its expression pattern during PC metastasis, tissue samples from the primary pancreatic tumor and metastases (from the same patient) in the lymph nodes, liver, lung and omentum from Stage IV PC patients were analyzed. To determine its association in the initiation of PC, tissues from PC patients containing pre-neoplastic lesions of varying grades were stained for MUC16. Finally, MUC16 expression was analyzed in 18 human PC cell lines. MUC16 is not expressed in the normal pancreatic ducts and is strongly upregulated in PC and detected in pancreatitis tissue. It is first detected in the high-grade pre-neoplastic lesions preceding invasive adenocarcinoma, suggesting that its upregulation is a late event during the initiation of this disease. MUC16 expression appears to be stronger in metastatic lesions when compared to the primary tumor, suggesting a role in PC metastasis. We have also identified PC cell lines that express MUC16, which can be used in future studies to elucidate its functional role in PC. Altogether, our results reveal that MUC16 expression is significantly increased in PC and could play a potential role in the progression of this disease.

Combining conventional and stroma-derived tumour markers in pancreatic ductal adenocarcinoma

“…The expression patterns of Ca 19-9, CEA, Ck18 and Ca 125 was in line with previous observations, including the weak stromal CEA staining, and the tendency of increasing Ca 125 expression with loss of differentiation [6,[34][35][36]. The absence of Ca 19-9 staining in two tumours probably stem from the fact that 5-10% of the population does not express the antigen.…”

Role of tetrahydrobiopterin in pulmonary vascular remodelling associated with pulmonary fibrosis

“…For immunohistochemical analysis of rat and human lungs, sections were immunostained with α-smooth muscle actin, sepiapterin reductase, GTP cyclohydrolase 1, eNOS and iNOS antibodies. Staining intensities of the various antibodies were scored and summed to obtain a composite score of 0–12, as described previously 16. Immunofluorescence of CD31, collagen type I, α-smooth muscle actin and vascular endothelial (VE)-cadherin was assessed in human pulmonary artery endothelial cells.…”

Validation of N-glycan markers that improve the performance of CA19-9 in pancreatic cancer

“…CA19-9 remains the only Food and Drug Administration (FDA)-approved biomarker for PC [5]. CA125 was also found to play an important role in the diagnosis and prognosis of PC [6]. Unfortunately, none is sufficiently sensitive or specific in the early diagnosis of PC individually until now.…”