A2B5 Cells from Human Glioblastoma have Cancer Stem Cell Properties

Brain Pathology - Tập 20 Số 1 - Trang 211-221 - 2010
Aurélie Tchoghandjian1, Nathalie Baeza2, Carole Colin2, Myriam Cayre3, Philippe Métellus4, Christophe Béclin3, L’Houcine Ouafik2, Dominique Figarella‐Branger2
1Université de la Méditerranée Aix-Marseille II, Faculté de Médecine la Timone, INSERM UMR911-CRO2, Angiogenèse, Invasivité et Microenvironnement Tumoral, Marseille cedex 05, France.
2Université de la Méditerranée Aix‐Marseille II, Faculté de Médecine la Timone, INSERM UMR911‐CRO2, Angiogenèse, Invasivité et Microenvironnement Tumoral.
3Université de la Méditerranée Aix‐Marseille II, Faculté de Sciences Luminy, UMR CNRS 6216 Institut de Biologie du Développement de Marseille‐Luminy.
4Assistance Publique‐Hôpitaux de Marseille, CHU Timone, Service de Neurochirurgie.

Tóm tắt

AbstractGlioblastomas, like other cancers, harbor small cell populations with the capability of sustaining tumor formation. These cells are referred to as cancer stem cells. We isolated cells expressing the surface marker A2B5 from three human glioblastomas (GBM) and showed that after grafting into nude mice, they generated dense and highly infiltrative tumors. Then, we extensively studied A2B5+ cells isolated from 11 human GBM. These cells display neurosphere‐like, self‐renewal, asymmetrical cell division properties and have multipotency capability. Stereotactic xenografts of dissociated A2B5+‐derived secondary spheres revealed that as few as 1000 cells produced a tumor. Moreover, flow cytometry characterization of A2B5+‐derived spheres revealed three distinct populations of cells: A2B5+/CD133+, A2B5+/CD133‐ and A2B5‐/CD133‐, with striking proportion differences among GBM. Both A2B5+/CD133+ and A2B5+/CD133‐ cell fractions displayed a high proliferative index, the potential to generate spheres and produced tumors in nude mice. Finally, we generated two green fluorescent protein‐cell lines that display—after serum induction—distinct proliferative and migratory properties, and differ in their CD133 level of expression. Taken together, our results suggest that transformed A2B5+ cells are crucial for the initiation and maintenance of GBM, although CD133 expression is more involved in determining the tumor's behavior.

Từ khóa


Tài liệu tham khảo

10.1038/nature05236

10.1158/0008-5472.CAN-06-4180

10.1016/j.ccr.2006.11.020

10.1111/j.1365-2990.2006.00740.x

10.1158/0008-5472.CAN-04-1364

10.1073/pnas.2036535100

10.1002/glia.10094

10.1038/labinvest.2008.57

10.1016/j.ydbio.2004.02.028

10.1073/pnas.0407893101

10.1038/nm837

10.1227/01.neu.0000316019.28421.95

10.1016/S0165-3806(01)00291-7

10.1158/0008-5472.CAN-07-0183

10.1126/science.1553558

Singh SK, 2003, Identification of a cancer stem cell in human brain tumors, Cancer Res, 63, 5821

10.1038/nature03128

10.1038/nrc1889

10.1002/ijc.23130

Thông tin
Thông tin xuất bản

Brain Pathology

Tập 20 Số 1

211-221

Thông tin tác giả