机构：[D]epartment of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden[2]Department of Cellular and Genetic Medicine,School of Basic Medical Sciences, Fudan University, Shanghai 200032, China[3]Kagoshima University Graduate School of Medical and Dental Sciences, 890-8520 Kagoshima, Japan[4]Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan 250033, China[5]Medicine and PharmacyResearch Center, Binzhou Medical University, Yantai 264003 Shandong, China[6]Unit of Computational Medicine, Department of Medicine, Center forMolecular Medicine, Karolinska Institute, 171 76 Stockholm, Sweden[7]Department of Urology, The University of Tokyo Hospital 7-3-1, Hongo, Bunkyo-ku,113-8655 Tokyo, Japan[8]Department of Medical Oncology and Cancer Institute, Shuguang Hospital Shanghai University of Traditional Chinese Medicine,Shanghai 201203, China[9]The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy ofMedical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China[10]State Key Laboratory of Ophthalmology, ZhongshanOphthalmic Center, Sun Yat-Sen University, Guangzhou 510060 Guangdong, China[11]Department of Cell Biology, Institute of Biomedicine, Jinan University,Guangzhou 510632, China[12]Department of Emergency Medicine, Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine,Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan 250012 Shandong, China.
FGF-2 displays multifarious functions in regulation of angiogenesis and vascular remodeling. However, effective drugs for treating FGF-2+ tumors are unavailable. Here we show that FGF-2 modulates tumor vessels by recruiting NG2+ pricytes onto tumor microvessels through a PDGFRβ-dependent mechanism. FGF-2+ tumors are intrinsically resistant to clinically available drugs targeting VEGF and PDGF. Surprisingly, dual targeting the VEGF and PDGF signaling produces a superior antitumor effect in FGF-2+ breast cancer and fibrosarcoma models. Mechanistically, inhibition of PDGFRβ ablates FGF-2-recruited perivascular coverage, exposing anti-VEGF agents to inhibit vascular sprouting. These findings show that the off-target FGF-2 is a resistant biomarker for anti-VEGF and anti-PDGF monotherapy, but a highly beneficial marker for combination therapy. Our data shed light on mechanistic interactions between various angiogenic and remodeling factors in tumor neovascularization. Optimization of antiangiogenic drugs with different principles could produce therapeutic benefits for treating their resistant off-target cancers.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
最新[2025]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Hosaka Kayoko,Yang Yunlong,Seki Takahiro,et al.Therapeutic paradigm of dual targeting VEGF and PDGF for effectively treating FGF-2 off-target tumors.[J].Nature communications.2020,11(1):3704.doi:10.1038/s41467-020-17525-6.
APA：
Hosaka Kayoko,Yang Yunlong,Seki Takahiro,Du Qiqiao,Jing Xu...&Cao Yihai.(2020).Therapeutic paradigm of dual targeting VEGF and PDGF for effectively treating FGF-2 off-target tumors..Nature communications,11,(1)
MLA：
Hosaka Kayoko,et al."Therapeutic paradigm of dual targeting VEGF and PDGF for effectively treating FGF-2 off-target tumors.".Nature communications 11..1(2020):3704
综合性期刊