title: Non-mitogenic form of acidic fibroblast growth factor protects against graft-versus-host disease without accelerating leukemia.
abstract: Acid fibroblast growth factor (aFGF) has been shown to prevent epithelial damage under various conditions, suggesting its potential to inhibit GVHD. However, because aFGF receptors are expressed on tumor cells, it may possibly offset the graft-vs.-tumor (GVT) effects of allogeneic bone marrow transplantation (allo-BMT). Here, we addressed these questions in a B6→B6D2F1 allo-BMT model. Although aFGF administration attenuated GVHD in non-leukemic recipients, aFGF treatment markedly accelerated death in mice that received recipient-type tumor (P815) cells along with allo- or syngeneic-BMT. Similar protection against GVHD was achieved by administration of a non-mitogenic form of aFGF (naFGF). Importantly, GVT effects were fully preserved in naFGF-treated recipients. Furthermore, aFGF, but not naFGF, significantly enhanced P815 cell proliferation both in vitro and in vivo. Our data indicate that the tumor-promoting, but not GVHD-protecting, effect of aFGF largely depends on its mitogenic activity, and suggest that naFGF may provide a safer approach to inhibiting GVHD in patients with malignancies.
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, PR China; Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA; Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, PR China.
authors.forename: Luqing
authors.initials: L
authors.lastname: Ren
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, PR China.
authors.forename: Qiaoyou
authors.initials: Q
authors.lastname: Weng
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, PR China.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, PR China.
authors.forename: Haishan
authors.initials: H
authors.lastname: Tian
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA; Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY, USA; First Hospital of Jilin University, Changchun, PR China. Electronic address: yy2324@cumc.columbia.edu.
authors.forename: Yong-Guang
authors.initials: YG
authors.lastname: Yang
authors.affiliation: Key Laboratory of Biotechnology Pharmaceutical Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, PR China. Electronic address: proflxk@163.com.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002460:Cell Line; D049109:Cell Proliferation; D016220:Fibroblast Growth Factor 1 / Q000008:administration & dosage*; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D051379:Mice
chemical_list: D016220:Fibroblast Growth Factor 1
keywords: Acidic fibroblast growth factor; GVHD; GVL; Mitogenic activity