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CD24(+) cells fuel rapid tumor growth and display high metastatic capacity
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 m...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479226/ https://www.ncbi.nlm.nih.gov/pubmed/26040280 http://dx.doi.org/10.1186/s13058-015-0589-9 |
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author | Rostoker, Ran Abelson, Sagi Genkin, Inna Ben-Shmuel, Sarit Sachidanandam, Ravi Scheinman, Eyal J. Bitton-Worms, Keren Orr, Zila Shen Caspi, Avishay Tzukerman, Maty LeRoith, Derek |
author_facet | Rostoker, Ran Abelson, Sagi Genkin, Inna Ben-Shmuel, Sarit Sachidanandam, Ravi Scheinman, Eyal J. Bitton-Worms, Keren Orr, Zila Shen Caspi, Avishay Tzukerman, Maty LeRoith, Derek |
author_sort | Rostoker, Ran |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-015-0589-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4479226 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44792262015-06-25 CD24(+) cells fuel rapid tumor growth and display high metastatic capacity Rostoker, Ran Abelson, Sagi Genkin, Inna Ben-Shmuel, Sarit Sachidanandam, Ravi Scheinman, Eyal J. Bitton-Worms, Keren Orr, Zila Shen Caspi, Avishay Tzukerman, Maty LeRoith, Derek Breast Cancer Res Research Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-015-0589-9) contains supplementary material, which is available to authorized users. BioMed Central 2015-06-04 2015 /pmc/articles/PMC4479226/ /pubmed/26040280 http://dx.doi.org/10.1186/s13058-015-0589-9 Text en © Rostoker et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Rostoker, Ran Abelson, Sagi Genkin, Inna Ben-Shmuel, Sarit Sachidanandam, Ravi Scheinman, Eyal J. Bitton-Worms, Keren Orr, Zila Shen Caspi, Avishay Tzukerman, Maty LeRoith, Derek CD24(+) cells fuel rapid tumor growth and display high metastatic capacity |
title | CD24(+) cells fuel rapid tumor growth and display high metastatic capacity |
title_full | CD24(+) cells fuel rapid tumor growth and display high metastatic capacity |
title_fullStr | CD24(+) cells fuel rapid tumor growth and display high metastatic capacity |
title_full_unstemmed | CD24(+) cells fuel rapid tumor growth and display high metastatic capacity |
title_short | CD24(+) cells fuel rapid tumor growth and display high metastatic capacity |
title_sort | cd24(+) cells fuel rapid tumor growth and display high metastatic capacity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479226/ https://www.ncbi.nlm.nih.gov/pubmed/26040280 http://dx.doi.org/10.1186/s13058-015-0589-9 |
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