Cancer initiating-cells are enriched in the CA9 positive fraction of primary cervix cancer xenografts

Delphine Tamara Marie-Egyptienne; Naz Chaudary; Tuula Kalliomäki; David William Hedley; Richard Peter Hill

doi:10.18632/oncotarget.13625

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Research Papers:

Cancer initiating-cells are enriched in the CA9 positive fraction of primary cervix cancer xenografts

Delphine Tamara Marie-Egyptienne _, Naz Chaudary, Tuula Kalliomäki, David William Hedley and Richard Peter Hill

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Oncotarget. 2017; 8:1392-1404. https://doi.org/10.18632/oncotarget.13625

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Abstract

Delphine Tamara Marie-Egyptienne1,3, Naz Chaudary1, Tuula Kalliomäki1,3, David William Hedley1,2,3,4, Richard Peter Hill1,3,5

1Ontario Cancer Institute/Princess Margaret Cancer Centre, University Health Network and Campbell Family Institute for Cancer Research, Toronto, Ontario, M5G2M9, Canada

2Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, M5G2M9, Canada

3Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

4Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, Ontario, Canada

5Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada

Correspondence to:

Richard Peter Hill, email: [email protected]

Keywords: cervix cancer, xenogratfs, stem cells, hypoxia, carbonic anhydrase 9

Received: August 20, 2016 Accepted: November 07, 2016 Published: November 25, 2016

ABSTRACT

Numerous studies have suggested that Cancer Initiating Cells (CIC) can be identified/enriched in cell populations obtained from solid tumors based on the expression of cell surface marker proteins. We used early passage primary cervix cancer xenografts to sort cells based on the expression of the intrinsic hypoxia marker Carbonic Anhydrase 9 (CA9) and tested their cancer initiation potential by limiting dilution assay. We demonstrated that CICs are significantly enriched in the CA9⁺ fraction in 5/6 models studied. Analyses of the expression of the stem cell markers Oct4, Notch1, Sca-1 & Bmi1 showed a trend toward an increase in the CA9⁺ populations, albeit not significant. We present evidence that enhanced autophagy does not play a role in the enhanced growth of the CA9⁺ cells. Our study suggests a direct in vivo functional link between hypoxic cells and CICs in primary cervix cancer xenografts.

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Research Papers:

Cancer initiating-cells are enriched in the CA9 positive fraction of primary cervix cancer xenografts

Abstract