| Upregulation of thrombospondin-1 and angiogenesis in an aggressive human pancreatic cancer cell line selected for high metastasis. | |
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MedLine Citation:
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PMID: 19584238 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Pancreatic cancer remains a leading cause of death despite its relatively low incidence. As in many other solid tumors, angiogenesis is critical to the growth and metastasis of this cancer. Through serial in vivo passages in mice, we have developed a highly aggressive variant of human pancreatic cancer cell line XPA-1 which shows more rapid primary tumor growth, faster time to metastasis, and more rapid lethality than the parental cell line. The high-metastatic variant developed a much denser tumor vasculature early during growth within the pancreas. Interestingly, examination of the in vitro growth of this aggressive variant yielded no significant difference from the parental cell line. Real-time PCR evaluation of genes involved in angiogenesis revealed a 24-fold increase in Thrombospondin-1 expression in cells derived from the high-metastatic variant when compared with the parental cell line. These findings provide direct evidence that elevated capability for angiogenesis, mediated by specific changes in gene expression, can lead to a large increase in cancer aggressiveness and resulting metastasis. These findings have important implications for the treatment of metastatic disease. |
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Authors:
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Michele K McElroy; Sharmeela Kaushal; Hop S Tran Cao; A R Moossa; Mark A Talamini; Robert M Hoffman; Michael Bouvet |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-07-07 |
Journal Detail:
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Title: Molecular cancer therapeutics Volume: 8 ISSN: 1538-8514 ISO Abbreviation: Mol. Cancer Ther. Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-07-15 Completed Date: 2009-10-19 Revised Date: 2013-02-19 |
Medline Journal Info:
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Nlm Unique ID: 101132535 Medline TA: Mol Cancer Ther Country: United States |
Other Details:
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Languages: eng Pagination: 1779-86 Citation Subset: IM |
Affiliation:
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Department of Surgery, University of California, San Diego, CA, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Ascites / etiology, pathology* Cell Line, Tumor Cell Proliferation Female Gene Expression Profiling Humans Mice Mice, Nude Mice, Transgenic Neoplasm Metastasis Neovascularization, Pathologic / metabolism* Oligonucleotide Array Sequence Analysis Pancreatic Neoplasms / blood supply*, metabolism, pathology RNA, Messenger / genetics, metabolism Reverse Transcriptase Polymerase Chain Reaction Thrombospondin 1 / genetics, metabolism* Up-Regulation Xenograft Model Antitumor Assays |
| Grant Support | |
ID/Acronym/Agency:
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CA103563/CA/NCI NIH HHS; CA109949-03/CA/NCI NIH HHS; R01 CA132971/CA/NCI NIH HHS; R01 CA142669/CA/NCI NIH HHS; R21 CA109949/CA/NCI NIH HHS; R21 CA135435/CA/NCI NIH HHS; R33 CA109949/CA/NCI NIH HHS; T32 CA121938/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; 0/Thrombospondin 1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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