Oncotarget

Research Papers:

Linneg Sca-1high CD49fhigh prostate cancer cells derived from the Hi-Myc mouse model are tumor-initiating cells with basal-epithelial characteristics and differentiation potential in vitro and in vivo

Achinto Saha, Jorge Blando, Irina Fernandez, Kaoru Kiguchi and John DiGiovanni _

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Oncotarget. 2016; 7:25194-25207. https://doi.org/10.18632/oncotarget.7535

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Abstract

Achinto Saha1,2,*, Jorge Blando1,2,*, Irina Fernandez2,3, Kaoru Kiguchi1,2, John DiGiovanni1,2

1Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78723, USA

2Dell Pediatric Research Institute, The University of Texas at Austin, Austin, TX 78723, USA

3Stem Cell Transplantation Department, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030, USA

*These authors contributed equally to this work

Correspondence to:

John DiGiovanni, email: [email protected]

Keywords: HMVP2 Cells, Hi-Myc mice, cancer stem cells, EMT, ventral prostate

Received: November 05, 2015     Accepted: January 29, 2016     Published: February 20, 2016

ABSTRACT

A cell line was established from ventral prostate (VP) tumors of one-year-old Hi-Myc mice. These cells, called HMVP2 cells, are LinnegSca-1highCD49fhigh with high CD44 and CD29 expression and express CK14, Sca-1 and CD49f (but not CK8), suggesting basal-epithelial characteristics. Furthermore, HMVP2 cells form spheroids and both the cells and spheroids produce tumors in syngeneic mice. After four days of culture, HMVP2 spheroids underwent a gradual transition from LinnegSca-1highCD49fhigh expression to LinnegSca-1lowCD49flow while a subpopulation of the cells retained the original LinnegSca-1highCD49fhigh expression pattern. Additional cell subpopulations expressing Lin positive markers were also present suggesting further differentiation of HMVP2 spheroids. Two additional highly tumorigenic cell lines (HMVP2A1 and HMVP2A2) were isolated from HMVP2 cells after subsequent tumor formation in FVB/N mice. Concurrently, we also established cell lines from the VP of 6 months old Hi-Myc mice (named as HMVP1) and FVB/N mice (called NMVP) having less aggressive growth properties compared to the other three cell lines. AR expression was reduced in HMVP2 cells compared to NMVP and HMVP1 cells and almost absent in HMVP2A1 and HMVP2A2 cells. These cell lines will provide valuable tools for further mechanistic studies as well as preclinical studies to evaluate preventive and/or therapeutic agents for prostate cancer.


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