TY - JOUR
T1 - Glioma-associated endothelial cells show evidence of replicative senescence
AU - Charalambous, Christiana
AU - Virrey, Jenilyn
AU - Kardosh, Adel
AU - Jabbour, Mark N.
AU - Qazi-Abdullah, Lubna
AU - Pen, Ligaya
AU - Zidovetzki, Raphael
AU - Schönthal, Axel H.
AU - Chen, Thomas C.
AU - Hofman, Florence M.
PY - 2007/4/1
Y1 - 2007/4/1
N2 - The innately programmed process of replicative senescence has been studied extensively with respect to cancer, but primarily from the perspective of tumor cells overcoming this stringent innate barrier and acquiring the capacity for unlimited proliferation. In this study, we focus on the potential role of replicative senescence affecting the non-transformed endothelial cells of the blood vessels within the tumor microenvironment. Based on the well-documented aberrant structural and functional features of blood vessels within solid tumors, we hypothesized that tumor-derived factors may lead to premature replicative senescence in tumor-associated brain endothelial cells (TuBEC). We show here that glioma tissue, but not normal brain tissue, contains cells that express the signature of replicative senescence, senescence-associated β-galactosidase (SA-β-gal), on CD31-positive endothelial cells. Primary cultures of human TuBEC stain for SA-β-gal and exhibit characteristics of replicative senescence, including increased levels of the cell cycle inhibitors p21 and p27, increased resistance to cytotoxic drugs, increased growth factor production, and inability to proliferate. These data provide the first demonstration that tumor-derived brain endothelial cells may have reached an end-stage of differentiation known as replicative senescence and underscore the need for anti-angiogenic therapies to target this unique tumor-associated endothelial cell population.
AB - The innately programmed process of replicative senescence has been studied extensively with respect to cancer, but primarily from the perspective of tumor cells overcoming this stringent innate barrier and acquiring the capacity for unlimited proliferation. In this study, we focus on the potential role of replicative senescence affecting the non-transformed endothelial cells of the blood vessels within the tumor microenvironment. Based on the well-documented aberrant structural and functional features of blood vessels within solid tumors, we hypothesized that tumor-derived factors may lead to premature replicative senescence in tumor-associated brain endothelial cells (TuBEC). We show here that glioma tissue, but not normal brain tissue, contains cells that express the signature of replicative senescence, senescence-associated β-galactosidase (SA-β-gal), on CD31-positive endothelial cells. Primary cultures of human TuBEC stain for SA-β-gal and exhibit characteristics of replicative senescence, including increased levels of the cell cycle inhibitors p21 and p27, increased resistance to cytotoxic drugs, increased growth factor production, and inability to proliferate. These data provide the first demonstration that tumor-derived brain endothelial cells may have reached an end-stage of differentiation known as replicative senescence and underscore the need for anti-angiogenic therapies to target this unique tumor-associated endothelial cell population.
KW - Endothelial cells
KW - Glioblastoma
KW - Microvasculature
KW - Senescence
KW - Tumor
UR - http://www.scopus.com/inward/record.url?scp=33947232856&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2006.12.027
DO - 10.1016/j.yexcr.2006.12.027
M3 - Article
C2 - 17291495
AN - SCOPUS:33947232856
SN - 0014-4827
VL - 313
SP - 1192
EP - 1202
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 6
ER -