Granulocyte colony-stimulating factor promotes tumor angiogenesis via increasing circulating endothelial progenitor cells and Gr1+CD11b+ cells in cancer animal models.
Recombinant granulocyte colony-stimulating factor (G-CSF) is used for cancer patients with myelosuppression induced by chemotherapy. G-CSF has been reported to progress tumor growth and angiogenesis, but the precise mechanism of tumor angiogenesis activated by G-CSF has not been fully clarified. N-terminal-mutated recombinant human G-CSF administration increased WBCs and neutrophils in peripheral blood and reduced bone marrow stromal cell-derived factor-1 in mice, indicating its biological relevance. Mice were inoculated with Lewis lung carcinoma cells (LLCs) or KLN205 cells and treated with G-CSF. G-CSF accelerated tumor growth and intratumoral vessel density, while it did not accelerate proliferation of LLCs, KLN205 cells or human umbilical vein endothelial cells in vitro. In the absence of tumors, G-CSF did not increase circulating cells that displayed phenotypic characteristics of endothelial progenitor cells (EPCs). In the presence of tumors, G-CSF increased circulating EPCs. In addition, G-CSF treatment increased immune suppressor and endothelial cell-differentiating Gr1+CD11b+ cells in tumor-bearing mice. We conclude that G-CSF promotes tumor growth by activating tumor angiogenesis via increasing circulating EPCs and Gr1+CD11b+ cells in cancer animal models.
Okazaki
Tatsuma
T
Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Seiryo-machi 1-1, Aoba-ku, Sendai 980-8574, Japan. tatsuma@geriat.med.tohoku.ac.jp
Ebihara
Satoru
S
Asada
Masanori
M
Kanda
Akio
A
Sasaki
Hidetada
H
Yamaya
Mutsuo
M
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000097:blood / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D038042:Myelopoiesis / Q000187:drug effects; D009389:Neovascularization, Pathologic / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D019707:Receptors, Chemokine / Q000378:metabolism; D011994:Recombinant Proteins; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism
D039481:CD11b Antigen; C503133:Gr-1 protein, mouse; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor