HIF2α is Involved in the Expansion of CXCR4-positive Cancer Stem-like Cells in Renal Cell Carcinoma

Overview

Journal Br J Cancer

Specialty Oncology

Date 2015 Oct 7

PMID 26439684

Citations 24

Authors

Carla Micucci

Giulia Matacchione

Debora Valli

Silvia Orciari

Alfonso Catalano

Affiliations

Soon will be listed here.

Abstract

Background: Hypoxia and the subsequent activation of hypoxia-inducible factor-2α (HIF2α) contribute to the progression of a variety of cancers. However, their role in the generation of renal cell carcinoma-derived stem cells has not been fully addressed.

Methods: A sphere formation assay, cell proliferation, RT-PCR, western blot, FACS, immunohistochemistry and tumour xenograft were used to study the role of HIF2α.

Results: Propagation of four renal cell carcinoma (RCC) cell lines (Caki-1, Caki-2, 786-O, 769-P) in anchorage-independent floating spheres led to the expansion of cells bearing the CXCR4 (CD184) surface marker. Inhibition of the CXCR4 pathway reduced sphere expansion. The enhanced self-renewal activity of the CXCR4-positive spheres was preceded by the upregulation of HIF2α. Knockdown of HIF2α abrogated CXCR4 expression and sphere formation. Finally, RCC-derived spheres showed an undifferentiated phenotype in vivo and formed subcutaneous tumours that highly expressed HIF2α and CXCR4. Inhibition of HIF2α abolished tumour growth in animal models.

Conclusions: These results suggest that the generation of RCC-derived CSCs involves the activation of HIF2α and may provide a foundation for the development of new strategies to prevent the induction of CSCs in RCC.

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