Increased expression of Cyr61 (CCN1) identified in peritoneal metastases from human pancreatic cancer
| Autor: | Shane E. Holloway, M. Raffat Jaber, Luc Girard, Carlton C. Barnett, Adam W. Beck, Rolf A. Brekken, Jason B. Fleming |
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| Rok vydání: | 2005 |
| Předmět: |
Pathology
medicine.medical_specialty Pancreatic disease Antibodies Neoplasm Mice Nude Adenocarcinoma Immediate-Early Proteins Metastasis Mice Pancreatic cancer Tumor Cells Cultured medicine Animals Cluster Analysis Humans RNA Messenger RNA Neoplasm Peritoneal Neoplasms Extracellular Matrix Proteins Reverse Transcriptase Polymerase Chain Reaction business.industry Microarray analysis techniques Matricellular protein medicine.disease Immunohistochemistry Primary tumor Gene Expression Regulation Neoplastic Pancreatic Neoplasms Reverse transcription polymerase chain reaction Real-time polymerase chain reaction Intercellular Signaling Peptides and Proteins Female Surgery business Neoplasm Transplantation Cysteine-Rich Protein 61 |
| Zdroj: | Journal of the American College of Surgeons. 200:371-377 |
| ISSN: | 1072-7515 |
| Popis: | Background Identification of extracellular matrix proteins (ECM) associated with tumor cell metastasis may generate targets for future therapy against pancreatic cancer metastases. We hypothesized that comparison of ECM-associated gene expression in primary and metastatic pancreatic tumors would identify ECM proteins associated with pancreatic metastasis. Study design A clinically relevant model of pancreatic cancer was used to generate RNA from primary and metastatic tumors; it was evaluated by microarray analysis with subsequent cluster analysis. Target genes (Cyr61 and integrins α v and β 3 ) identified by microarray analysis were confirmed by reverse transcription polymerase chain reaction and immunohistochemistry analysis. Results Peritoneal metastases at sites distant from the primary tumor were present in all animals bearing orthotopic tumors. High-density microarray comparison of gene expression in metastases versus primary pancreatic tumors identified a greater than twofold increase in the expression of Cyr61, a secreted matricellular protein that binds to integrins. Reverse transcription polymerase chain reaction confirmed the microarray results, and immunohistochemistry analysis demonstrated increased Cyr61 protein and persistent α v β 3 expression in peritioneal metastases. Additionally, immunohistochemistry demonstrated increased collocalization of Cyr61 and α v in metastases relative to primary tumor. Conclusions The ECM protein Cyr61 shows increased expression in metastatic lesions in a clinically relevant model of pancreatic adenocarcinoma. Protein analysis confirms the microarray results and collocalization of Cyr61, and α v suggests that interaction between Cyr61 and α v β 3 promotes formation of peritoneal metastases. |
| Databáze: | OpenAIRE |
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