title: Granulocyte-macrophage colony-stimulating factor increases tumor growth and angiogenesis directly by promoting endothelial cell function and indirectly by enhancing the mobilization and recruitment of proangiogenic granulocytes.
abstract: Granulocyte-macrophage colony-stimulating factor has been widely used as an adjuvant therapy for cancer patients exhibiting myelosuppression induced by chemotherapy or radiotherapy. However, the effects of granulocyte-macrophage colony-stimulating factor on tumor growth, as well as its precise mechanism, are still controversial due to inconsistent evidence. This study investigated the effect of exogenous granulocyte-macrophage colony-stimulating factor on the growth of B16 melanoma, S180 sarcoma, and U14 cervical carcinoma in mice. The angiogenesis and recruitment of bone-marrow-derived cells were analyzed in tumor tissues. Interactions among granulocyte-macrophage colony-stimulating factor, bone-marrow-derived cells, and B16 tumor cells were investigated in vitro. Proangiogenic types of bone-marrow-derived cells in blood were assessed both in vivo and in vitro. The results showed that granulocyte-macrophage colony-stimulating factor markedly facilitated the growth of B16 and S180 tumors, but not U14 tumors. Granulocyte-macrophage colony-stimulating factor increased the densities of blood vessels and the number of bone-marrow-derived cells in B16 tumor tissues. The granulocyte-macrophage colony-stimulating factor-induced enhancement of tumor cell proliferation was mediated by bone-marrow-derived cells in vitro. Meanwhile, a distinct synergistic effect on endothelial cell function between granulocyte-macrophage colony-stimulating factor and bone-marrow-derived cells was observed. After separating two types of bone-marrow-derived cells, granulocyte-macrophage colony-stimulating factor-induced enhancement of tumor growth and angiogenesis in vivo was mediated by proangiogenic cells in granulocytes, but not monocytes, with CD11b+, vascular endothelial growth factor receptor 2, and C-X-C chemokine receptor 4 granulocytes possibly involved. These data suggest that granulocyte-macrophage colony-stimulating factor contributes to the growth and angiogenesis of certain types of tumor, and these mechanisms are probably mediated by proangiogenic cells in granulocytes. Applying granulocyte-macrophage colony-stimulating factor may attenuate the antitumor effects of chemotherapy and radiotherapy in certain types of tumor.
authors.affiliation: 1 First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Qiaowei
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: 1 First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Xueqian
authors.initials: X
authors.lastname: Li
authors.affiliation: 1 First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Cheng
authors.affiliation: 2 China Resources Sanjiu Medical & Pharmaceutical Co. Ltd., Shenzhen, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Cui
authors.affiliation: 1 First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Yingcheng
authors.initials: Y
authors.lastname: Zhuo
authors.affiliation: 1 First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Ma
authors.affiliation: 1 First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhao
authors.affiliation: 1 First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Zhao
authors.affiliation: 1 First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Xuanlin
authors.initials: X
authors.lastname: Liu
authors.affiliation: 1 First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Feng
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D002642:Chick Embryo; D042783:Endothelial Cells / Q000187:drug effects*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006098:Granulocytes / Q000187:drug effects* / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011897:Random Allocation
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: Angiogenesis; ganulocyte-macrophage colony-stimulating factor; tumor growth