期刊
CYTOMETRY PART A
卷 79A, 期 9, 页码 672-683出版社
WILEY-BLACKWELL
DOI: 10.1002/cyto.a.21103
关键词
side population; stem cells; Hedgehog; smoothened; Hoechst 33342; flow cytometry
资金
- Spanish Ministry of Health [PI081132, PI070098]
- Departamento de Salud del Gobierno de Navarra [9/07]
- Caja Navarra [08/13912]
- Fondo de Investigacion Sanitaria, Madrid [PI081849]
- Asociacion de Amigos de la Universidad de Navarra
- Fundacion Universitaria de Navarra, Pamplona
The Sonic Hedgehog (Hh) pathway has been implicated in the maintenance of stem or progenitor cells in many adult tissues. Importantly, abnormal Hh pathway activation is also associated with initiation of neoplasia, but its role in tumor growth is still unclear. Here, we demonstrate that cyclopamine, a plant-derived alkaloid product used to inhibit the Hh signaling pathway, reduces the Side Population (SP) obtained by Hoechst 33342 (Ho342) dye measurements. In addition, cyclopamine is able to modulate, along with oxysterols and other products, the ABCG2 transporter by increasing Ho342 and mitoxantrone uptake. Therefore, if the SP is solely measured as a Ho342 dye extruding fraction, this may be significantly modulated by the inhibition of ABCG2 transport fraction, independently from the action of cyclopamine on the Hh pathway. Our results indicate that ABCG2 may act in the upstream regulation of the Hh signaling pathway to protect the sternness of the SP compartment, giving support to the cancer stem cell hypothesis and suggesting that ABCG2 is not only critical for increased resistance to anticancer agents. (C) 2011 international Society for Advancement of Cytometry
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