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In vivo evolution of tumor-derived endothelial cells

McGuire, TF and Sajithlal, GB and Lu, J and Nicholls, RD and Prochownik, EV (2012) In vivo evolution of tumor-derived endothelial cells. PLoS ONE, 7 (5).

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The growth of a malignant tumor beyond a certain, limited size requires that it first develop an independent blood supply. In addition to providing metabolic support, this neovasculature also allows tumor cells to access the systemic circulation, thus facilitating metastatic dissemination. The neovasculature may originate either from normal blood vessels in close physical proximity to the tumor and/or from the recruitment of bone marrow-derived endothelial cell (EC) precursors. Recent studies have shown that human tumor vasculature ECs may also arise directly from tumor cells themselves and that the two populations have highly similar or identical karyotypes. We now show that, during the course of serial in vivo passage, these tumor-derived ECs (TDECs) progressively acquire more pronounced EC-like properties. These include higher-level expression of EC-specific genes and proteins, a greater capacity for EC-like behavior in vitro, and a markedly enhanced propensity to incorporate into the tumor vasculature. In addition, both vessel density and size are significantly increased in neoplasms derived from mixtures of tumor cells and serially passaged TDECs. A comparison of early- and late-passage TDECs using whole-genome single nucleotide polymorphism profiling showed the latter cells to have apparently evolved by a process of clonal expansion of a population with a distinct pattern of interstitial chromosomal gains and losses affecting a relatively small number of genes. The majority of these have established roles in vascular development, tumor suppression or epithelial-mesenchymal transition. These studies provide direct evidence that TDECs have a strong evolutionary capacity as a result of their inherent genomic instability. Consequently such cells might be capable of escaping anti-angiogenic cancer therapies by generating resistant populations. © 2012 McGuire et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
McGuire, TFtfm1@pitt.eduTFM1
Sajithlal, GB
Lu, J
Nicholls, RDrdn4@pitt.eduRDN4
Prochownik, EVevp4@pitt.eduEVP4
ContributionContributors NameEmailPitt UsernameORCID
Centers: Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute
Date: 18 May 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 5
DOI or Unique Handle: 10.1371/journal.pone.0037138
Schools and Programs: School of Public Health > Human Genetics
School of Medicine > Microbiology and Molecular Genetics
Refereed: Yes
MeSH Headings: Cell Differentiation--physiology; Cell Lineage--physiology; Cytogenetic Analysis; Endothelial Cells--metabolism; Endothelial Cells--physiology; Gene Expression Regulation, Neoplastic--genetics; Gene Expression Regulation, Neoplastic--physiology; Genomic Instability--physiology; Humans; Neoplasms--blood supply; Neovascularization, Pathologic--physiopathology; Polymorphism, Single Nucleotide--genetics; Real-Time Polymerase Chain Reaction
Other ID: NLM PMC3356387
PubMed Central ID: PMC3356387
PubMed ID: 22623986
Date Deposited: 04 Oct 2012 14:16
Last Modified: 19 Feb 2018 22:55


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