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Breast Cancer Research
Published in: Breast Cancer Research 1/2015

Open Access 01-12-2015 | Research article

CD24+ cells fuel rapid tumor growth and display high metastatic capacity

Authors: Ran Rostoker, Sagi Abelson, Inna Genkin, Sarit Ben-Shmuel, Ravi Sachidanandam, Eyal J. Scheinman, Keren Bitton-Worms, Zila Shen Orr, Avishay Caspi, Maty Tzukerman, Derek LeRoith

Published in: Breast Cancer Research | Issue 1/2015

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Abstract

Introduction

Breast tumors are comprised of distinct cancer cell populations which differ in their tumorigenic and metastatic capacity. Characterization of cell surface markers enables investigators to distinguish between cancer stem cells and their counterparts. CD24 is a well-known cell surface marker for mammary epithelial cells isolation, recently it was suggested as a potential prognostic marker in a wide variety of malignancies. Here, we demonstrate that CD24+ cells create intra-tumor heterogeneity, and display highly metastatic properties.

Methods

The mammary carcinoma Mvt1 cells were sorted into CD24− and CD24+ cells. Both subsets were morphologically and phenotypically characterized, and tumorigenic capacity was assessed via orthotopic inoculation of each subset into the mammary fat pad of wild-type and MKR mice. The metastatic capacity of each subset was determined with the tail vein metastasis assay. The role of CD24 in tumorigenesis was further examined with shRNA technology. GFP-labeled cells were monitored in vivo for differentiation. The genetic profile of each subset was analyzed using RNA sequencing.

Results

CD24+ cells displayed a more spindle-like cytoplasm. The cells formed mammospheres in high efficiency and CD24+ tumors displayed rapid growth in both WT and MKR mice, and were more metastatic than CD24- cells. Interestingly, CD24-KD in CD24+ cells had no effect both in vitro and in vivo on the various parameters studied. Moreover, CD24+ cells gave rise in vivo to the CD24− that comprised the bulk of the tumor. RNA-seq analysis revealed enrichment of genes and pathways of the extracellular matrix in the CD24+ cells.

Conclusion

CD24+ cells account for heterogeneity in mammary tumors. CD24 expression at early stages of the cancer process is an indication of a highly invasive tumor. However, CD24 is not a suitable therapeutic target; instead we suggest here new potential targets accounting for early differentiated cancer cells tumorigenic capacity.
Appendix
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Metadata
Title
CD24+ cells fuel rapid tumor growth and display high metastatic capacity
Authors
Ran Rostoker
Sagi Abelson
Inna Genkin
Sarit Ben-Shmuel
Ravi Sachidanandam
Eyal J. Scheinman
Keren Bitton-Worms
Zila Shen Orr
Avishay Caspi
Maty Tzukerman
Derek LeRoith
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2015
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-015-0589-9

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