17Beta-estradiol mobilizes bone marrow-derived endothelial progenitor cells to tumors.
Neovascularization is critical for tumor growth and development. The cellular mediators for this process are yet to be defined. We discovered that bone marrow-derived endothelial progenitor cells (BM-EPC), having the phenotype (CD133+, CD34+, VEGFR-2+), initiate neovascularization in response to TG1-1 mammary cells implanted in the inguinal mammary gland of Tie-2 GFP transgenic mice. The fluorescence tag allowed for tracing the migration of green fluorescent protein-tagged endothelial progenitor cells to tumor tissues. We discovered that 17-beta estradiol supplementation of ovariectomized mice significantly enhanced BM-EPC-induced neovascularization and secretion of angiogenic factors within the tumor microenvironment. Cell-based system analyses showed that estrogen-stimulated BM-EPCs secreted paracrine factors which enhanced TG1-1 cell proliferation and migration. Furthermore, TG1-1 cell medium supplemented with estrogen-induced BM-EPC mediated tubulogenesis, which was an experimental in vivo representation of the neovasculature. Our data provide evidence of BM-EPC mammary tumor cell interactions and identify a novel cellular mediator of tumor progression that can be exploited clinically.
Suriano
Robert
R
Department of Microbiology and Immunology, New York Medical College, Valhalla, New York 10595, USA.
Chaudhuri
Devyani
D
Johnson
Raja Singh
RS
Lambers
Erin
E
Ashok
Badithe T
BT
Kishore
Raj
R
Tiwari
Raj K
RK
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005456:Fluorescent Dyes; D020782:Matrix Metalloproteinases / Q000235:genetics; D051379:Mice; D009374:Neoplasms, Experimental / Q000098:blood supply*; D009389:Neovascularization, Pathologic; D010052:Ovariectomy
D005456:Fluorescent Dyes; D004958:Estradiol; D020782:Matrix Metalloproteinases