Journal
CANCER LETTERS
Volume 352, Issue 2, Pages 179-186Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2014.06.012
Keywords
Prostate cancer; Circulating tumor cells; EMT; MMP-2; Metastasis; Drug resistance
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Funding
- National Institutes of Health (NIH) [CA122985, Prostate SPORE CA90386, NIH T32 AG000260]
- Walter S. And Lucienne Driskill Graduate Program in Life Sciences at Northwestern University
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With prostate cancer (PCa), circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) portend a poor clinical prognosis. Their unknown biology precludes rational therapeutic design. We demonstrate that CTC and DTC cell lines, established from mice bearing human PCa orthotopic implants, exhibit increased cellular invasion in vitro, increased metastasis in mice, and express increased epithelial to mesenchymal transition biomarkers. Further, they are selectively resistant to growth inhibition by mitoxantrone-like agents. These findings demonstrate that CTC formation is accompanied by phenotypic progression without obligate reversion. Their increased metastatic potential, selective therapeutic resistance, and differential expression of potential therapeutic targets provide a rational basis to test further interventions. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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