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  • 1
    Keywords: APOPTOSIS ; CANCER ; CANCER CELLS ; CELLS ; EXPRESSION ; GROWTH ; INVASION ; proliferation ; SURVIVAL ; tumor ; carcinoma ; CELL-PROLIFERATION ; Germany ; human ; FOLLOW-UP ; DISEASE ; liver ; PROTEIN ; MOLECULES ; TISSUE ; TUMORS ; TIME ; PATIENT ; MARKER ; DONOR ; prognosis ; TISSUES ; MOLECULE ; BREAST-CANCER ; GLYCOPROTEIN ; IDENTIFICATION ; MALIGNANCIES ; METASTASIS ; metastases ; PCR ; CANCER-CELLS ; ADHESION ; MIGRATION ; CANCER-PATIENTS ; adenocarcinoma ; LIVER METASTASES ; CANCER PATIENTS ; HEALTHY ; pancreatic cancer ; chronic pancreatitis ; SERUM ; ELISA ; MALIGNANCY ; RECOMBINANT ; PANCREATIC-CANCER ; TUMOR-GROWTH ; DUCTAL ADENOCARCINOMA ; INCREASE ; extracellular matrix ; REAL-TIME ; cell adhesion ; cell proliferation ; LEVEL ; OSTEOPONTIN ; SERUM-LEVELS ; downregulation ; function ; BLOCKADE ; IMMUNOHISTOCHEMICAL ANALYSIS ; INVASIVENESS ; lymph node ; LYMPH-NODE ; PLASMA OSTEOPONTIN ; restricting ; serum marker
    Abstract: Pancreatic ductal adenocarcinoma ( PDAC) is one of the most aggressive malignancies, with an overall 5-year survival rate of less than 5%. Invasive tumor growth and early metastasis are two important reasons for this dismal prognosis. Osteopontin ( OPN) is a secretory protein with a variety of functions, for example in cell adhesion and migration, inflammatory reaction and apoptosis. In this study the functional role of OPN in human pancreatic cancer and its potential use as a disease marker were analyzed. By real time quantitative PCR, there was a 2.2- fold and 1.6- fold increase of OPN mRNA in pancreatic cancers (n = 23) and chronic pancreatitis samples (n = 22), respectively, compared to normal pancreatic tissues (n = 20). Immunohistochemical analysis demonstrated OPN staining in 60% of the primary pancreatic tumors and in 72% of the lymph node and liver metastases. ELISA analysis of serum samples obtained from pancreatic cancer patients (n = 70), chronic pancreatitis patients (n = 12), and healthy donors (n = 20) showed a 1.6-fold increase in OPN serum levels in patients with tumors and a 1.9-fold increase in patients with chronic pancreatitis. Recombinant human OPN significantly increased the invasiveness of pancreatic cancer cells, without having any impact on cell proliferation. In addition, downregulation of OPN by specific siRNA molecules decreased pancreatic cancer cell invasion. In conclusion, OPN serum levels in pancreatic cancer and chronic pancreatitis patients are not significantly different, thereby restricting its role as a prognostic or follow-up marker. Our results do suggest, however, that blockade of OPN might be useful as a therapeutic approach to inhibit invasion and metastasis of pancreatic cancer cells
    Type of Publication: Journal article published
    PubMed ID: 15970685
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  • 2
    Keywords: CANCER ; CANCER CELLS ; CELLS ; ENDOTHELIAL-CELLS ; EXPRESSION ; GROWTH ; IN-VITRO ; INVASION ; proliferation ; tumor ; TUMOR-CELLS ; Germany ; VITRO ; DISEASE ; GENE ; GENES ; TISSUE ; TUMORS ; PATIENT ; prognosis ; INDUCTION ; CONTRAST ; fibroblasts ; GLYCOPROTEIN ; PROGRESSION ; immunohistochemistry ; ASSAY ; CANCER-CELLS ; EXTRACELLULAR-MATRIX ; NEOPLASTIC PROGRESSION ; POLYMERASE-CHAIN-REACTION ; adenocarcinoma ; OVEREXPRESSION ; POOR-PROGNOSIS ; pancreatic cancer ; chronic pancreatitis ; HUMAN BREAST-CANCER ; SERUM ; MATRIX ; quantitative polymerase chain reaction ; PANCREATIC-CANCER ; DUCTAL ADENOCARCINOMA ; extracellular matrix ; OLIGONUCLEOTIDE ; interaction ; TARGET GENE ; TARGET GENES ; ANTISENSE OLIGONUCLEOTIDE ; MALIGNANT-TUMORS ; EXTRACELLULAR-MATRIX PROTEINS ; DISEASE PROGRESSION ; CYSTEINE SPARC ; DEGRADING PROTEASES ; ESOPHAGEAL-CARCINOMA ; I COLLAGEN ; MATRICELLULAR PROTEIN ; SPARC EXPRESSION
    Abstract: Objective: We sought to examine the expression and functional role of osteonectin in primary and metastatic pancreatic ductal adenocarcinoma (PDAC). Background: The glycoprotein osteonectin plays a vital role in cell-matrix interactions and is involved in various biologic processes. Overexpression of osteonectin is present in malignant tumors and correlates with disease progression and poor prognosis. Methods: Expression of osteonectin was analyzed by quantitative polymerase chain reaction and immunohistochemistry in pancreatic tissues and by enzyme-linked immunosorbent assay in the serum of patients and donors. Recombinant osteonectin and specific antisense oligonucleotides were used to examine the effects of osteonectin on induction of target genes, and on proliferation and invasiveness of pancreatic cancer cells. Results: There was a 31-fold increase in osteonectin mRNA levels in PDAC and a 16-fold increase in chronic pancreatitis as compared with the normal pancreas (P 〈 0.01). By immunohistochemistry, faint immunoreactivity was detected in the normal pancreas. In contrast, strong staining of the cancer cells was observed in addition to extensive osteonectin immunoreactivity in surrounding fibroblasts and in the extracellular matrix. In metastatic tissues, strong immunoreactivity was observed in fibroblasts and in extracellular matrix surrounding metastatic cancer cells, whereas the signal was absent in most tumor cells. In vitro studies showed that osteonectin was able to inhibit cancer cell growth while promoting invasiveness of pancreatic tumor cells. Conclusion: Osteonectin is markedly overexpressed in pancreatic cancer and has the potential to increase the invasiveness of pancreatic cancer cells
    Type of Publication: Journal article published
    PubMed ID: 16041213
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  • 3
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    German Medical Science; Düsseldorf, Köln
    In:  122. Kongress der Deutschen Gesellschaft für Chirurgie; 20050405-20050408; München; DOC05dgch3260 /20050615/
    Publication Date: 2005-06-16
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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