TY - JOUR
T1 - B7-H4 is preferentially expressed in non-dividing brain tumor cells and in a subset of brain tumor stem-like cells
AU - Yao, Yu
AU - Wang, Xiaomei
AU - Jin, Kunlin
AU - Zhu, Jianhong
AU - Wang, Yin
AU - Xiong, Sidong
AU - Mao, Ying
AU - Zhou, Liangfu
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2008
Y1 - 2008
N2 - B7-H4, a newly discovered member of B7 family that negatively regulates T cell-mediated immunity, may facilitate tumor progression by undermining host immunity. Recent studies show that brain tumor stem-like cells (TSCs) contribute to tumorigenesis. However, the relationship between B7-H4 and the clinical behavior of brain TSCs remains unclear. In this study, we found that B7-H4 was expressed in cultured tumor cells from human gliomas (n = 5) and medulloblastomas (n = 3). Double immunostaining indicated that B7-H4 was primarily restricted to non-dividing (Ki67-) cultured tumor cells. Tumor cells cultured under medium conditions favoring the growth of neural stem cells were able to form primary and secondary spheres, along with expression of neural stem/progenitor cell markers. These cells differentiated into different neural lineages when cultured in differentiation medium, indicating that these cells have TSCs characteristics. Double immunostaining showed that TSCs consisted of proliferative (Ki67+) and quiescent (Ki67-) cells. We also found that B7-H4 was expressed in a small population of CD133+ cells sorted by flow cytometry. Interestingly, both CD133+ and CD133- cells were tumorigenic in SCID mice in vivo. However, CD133+ cells-initiated glioblastomas showed a higher proliferatio index, compared to CD133- cells-induced glioblastomas in vivo. Secondary glioma cells derived from CD133+ or CD133- cell xenografts expressed B7-H4 as well. Our data suggest B7-H4 is preferentially expressed in non-dividing brain tumor cells and in a subpopulation of brain TSCs, and CD133- tumor cells also have the capacity to initiate brain formation in vivo.
AB - B7-H4, a newly discovered member of B7 family that negatively regulates T cell-mediated immunity, may facilitate tumor progression by undermining host immunity. Recent studies show that brain tumor stem-like cells (TSCs) contribute to tumorigenesis. However, the relationship between B7-H4 and the clinical behavior of brain TSCs remains unclear. In this study, we found that B7-H4 was expressed in cultured tumor cells from human gliomas (n = 5) and medulloblastomas (n = 3). Double immunostaining indicated that B7-H4 was primarily restricted to non-dividing (Ki67-) cultured tumor cells. Tumor cells cultured under medium conditions favoring the growth of neural stem cells were able to form primary and secondary spheres, along with expression of neural stem/progenitor cell markers. These cells differentiated into different neural lineages when cultured in differentiation medium, indicating that these cells have TSCs characteristics. Double immunostaining showed that TSCs consisted of proliferative (Ki67+) and quiescent (Ki67-) cells. We also found that B7-H4 was expressed in a small population of CD133+ cells sorted by flow cytometry. Interestingly, both CD133+ and CD133- cells were tumorigenic in SCID mice in vivo. However, CD133+ cells-initiated glioblastomas showed a higher proliferatio index, compared to CD133- cells-induced glioblastomas in vivo. Secondary glioma cells derived from CD133+ or CD133- cell xenografts expressed B7-H4 as well. Our data suggest B7-H4 is preferentially expressed in non-dividing brain tumor cells and in a subpopulation of brain TSCs, and CD133- tumor cells also have the capacity to initiate brain formation in vivo.
KW - B7-H4
KW - Brain
KW - Glioma
KW - Medulloblastoma
KW - Tumor stem-like cells
UR - http://www.scopus.com/inward/record.url?scp=48749090387&partnerID=8YFLogxK
U2 - 10.1007/s11060-008-9601-x
DO - 10.1007/s11060-008-9601-x
M3 - Article
C2 - 18478183
AN - SCOPUS:48749090387
VL - 89
SP - 121
EP - 129
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
SN - 0167-594X
IS - 2
ER -