期刊
CANCER LETTERS
卷 429, 期 -, 页码 78-88出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2018.04.042
关键词
Secretome; Cancer stem-like cells; Mesenchymal stem cells; Cytogenetic; Interleukin-6; Hepatocyte growth factor
类别
资金
- Ministry of Economy and Competitiveness, Instituto de Salud Carlos III (FEDER funds) [PIE16/00045, DTS17/00087]
- Ministerio de Economia y Competitividad (MINECO, FEDER funds) [MAT2015-62644.C2.2.R]
- Fundacion Publica Andaluza Progreso y Salud
- Consejeria de Salud Junta de Andalucia
- JANNSSEN CILAG, S.A. [PI-0533-2014]
- Chair Doctors Galera-Requena in cancer stem cell research [CMC-CTS963]
Cancer stem cells (CSCs) are responsible for tumor initiation, metastasis and cancer recurrence, however the involvement of microenvironment is crucial. Here, we have analyzed how human mesenchymal stem cells (MSCs)-derived conditioned medium (CM) affect colon and melanoma CSCs enrichment and maintenance. Our results strongly suggest that the secretome of CM-MSCs selects and maintains subpopulations with high expression of CSCs markers and ALDH1 activity, low proliferation rates with G1 phase arrest, and notably retain in vivo these properties. Cytogenetic analyses indicated that CM-cultured cells contain alterations in chromosome 17 (17q25). Subsequent SKY-FISH analyses suggested that genes located in 17q25 might be involved in stem-cell maintenance. The characterization of secreted proteins present in CM-MSCs revealed that four cytokines and seven growth factors are directly linked to the CSCs enrichment reported in this study. Further analyses revealed that the combination of just IL6 and HGF is enough to provide cancer cells with better sternness properties. In conclusion, this study demonstrates how specific chromosomal alterations present in CSCs subpopulations might represent an advantage for their in vitro maintenance and in vivo sternness properties.
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