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Cancer Lett. 2014 Oct 1;352(2):179-86. doi: 10.1016/j.canlet.2014.06.012. Epub 2014 Jul 10.

Circulating tumor cells exhibit a biologically aggressive cancer phenotype accompanied by selective resistance to chemotherapy.

Author information

1
Department of Medicine, Northwestern University, United States.
2
Department of Medicine, Northwestern University, United States; Robert H. Lurie Cancer Center, Northwestern University, United States; Center for Molecular Innovation and Drug Discovery, Northwestern University, United States. Electronic address: r-bergan@northwestern.edu.

Abstract

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.

KEYWORDS:

Circulating tumor cells; Drug resistance; EMT; MMP-2; Metastasis; Prostate cancer

PMID:
25016063
PMCID:
PMC4139115
DOI:
10.1016/j.canlet.2014.06.012
[Indexed for MEDLINE]
Free PMC Article

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