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A Novel Platform for Detection of CK+ and CK− CTCs

Chad V. Pecot, Farideh Z. Bischoff, Julie Ann Mayer, Karina L. Wong, Tam Pham, Justin Bottsford-Miller, Rebecca L. Stone, Yvonne G. Lin, Padmavathi Jaladurgam, Ju Won Roh, Blake W. Goodman, William M. Merritt, Tony J. Pircher, Stephen D. Mikolajczyk, Alpa M. Nick, Joseph Celestino, Cathy Eng, Lee M. Ellis, Michael T. Deavers and Anil K. Sood
Chad V. Pecot
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Farideh Z. Bischoff
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Julie Ann Mayer
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Karina L. Wong
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Tam Pham
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Justin Bottsford-Miller
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Rebecca L. Stone
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Yvonne G. Lin
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Padmavathi Jaladurgam
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Ju Won Roh
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Blake W. Goodman
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William M. Merritt
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Tony J. Pircher
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Stephen D. Mikolajczyk
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Alpa M. Nick
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Joseph Celestino
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Cathy Eng
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Lee M. Ellis
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Michael T. Deavers
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Anil K. Sood
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DOI: 10.1158/2159-8290.CD-11-0215 Published December 2011
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Abstract

Metastasis is a complex, multistep process that begins with the epithelial–mesenchymal transition (EMT). Circulating tumor cells (CTC) are believed to have undergone EMT and thus lack or express low levels of epithelial markers commonly used for enrichment and/or detection of such cells. However, most current CTC detection methods target only EpCAM and/or cytokeratin (CK) to enrich epithelial CTCs, resulting in failure to recognize other, perhaps more important, CTC phenotypes that lack expression of these markers. Here, we describe a population of complex aneuploid CTCs that do not express CK or CD45 antigen in patients with breast, ovarian, or colorectal cancer. These cells were not observed in healthy subjects. We show that the primary epithelial tumors were characterized by similar complex aneuploidy, indicating conversion to an EMT phenotype in the captured cells. Collectively, our study provides a new method for highly efficient capture of previously unrecognized populations of CTCs.

Significance: Current assays for CTC capture likely miss populations of cells that have undergone EMT. Capture and study of CTCs that have undergone EMT would allow a better understanding of the mechanisms driving metastasis. Cancer Discovery; 1(7); 580–86. ©2011 AACR.

This article is highlighted in the In This Issue feature, p. 539

Footnotes

  • Note: Supplementary data for this article are available at Cancer Discovery Online (http://www.cancerdiscovery.aacrjournals.org).

  • Received August 29, 2011.
  • Revision received October 17, 2011.
  • Accepted October 31, 2011.
  • ©2011 American Association for Cancer Research.
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Cancer Discovery: 1 (7)
December 2011
Volume 1, Issue 7
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A Novel Platform for Detection of CK+ and CK− CTCs
Chad V. Pecot, Farideh Z. Bischoff, Julie Ann Mayer, Karina L. Wong, Tam Pham, Justin Bottsford-Miller, Rebecca L. Stone, Yvonne G. Lin, Padmavathi Jaladurgam, Ju Won Roh, Blake W. Goodman, William M. Merritt, Tony J. Pircher, Stephen D. Mikolajczyk, Alpa M. Nick, Joseph Celestino, Cathy Eng, Lee M. Ellis, Michael T. Deavers and Anil K. Sood
Cancer Discov December 1 2011 (1) (7) 580-586; DOI: 10.1158/2159-8290.CD-11-0215

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A Novel Platform for Detection of CK+ and CK− CTCs
Chad V. Pecot, Farideh Z. Bischoff, Julie Ann Mayer, Karina L. Wong, Tam Pham, Justin Bottsford-Miller, Rebecca L. Stone, Yvonne G. Lin, Padmavathi Jaladurgam, Ju Won Roh, Blake W. Goodman, William M. Merritt, Tony J. Pircher, Stephen D. Mikolajczyk, Alpa M. Nick, Joseph Celestino, Cathy Eng, Lee M. Ellis, Michael T. Deavers and Anil K. Sood
Cancer Discov December 1 2011 (1) (7) 580-586; DOI: 10.1158/2159-8290.CD-11-0215
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