title: Stromal cells attenuate the cytotoxicity of imatinib on Philadelphia chromosome-positive leukemia cells by up-regulating the VE-cadherin/β-catenin signal.
abstract: β-Catenin is a key regulator of leukemia stem cell maintenance and drug resistance. Herein, we investigated the protective effects of the stromal cell-mediated VE-cadherin-β-catenin signal on Ph+ leukemia cells during imatinib treatment. We found stromal cells could desensitize imatinib and up-regulate VE-cadherin expression on Ph+ leukemia cells (K562 and SUP-B15 cells), which further stabilized and activated β-catenin. Knockdown of VE-cadherin with shRNA diminished the β-catenin protein and partly resensitized Ph+ leukemia cells to imatinib despite the presence of stromal cells, suggesting VE-cadherin is a potential target in the treatment of Ph+ leukemia.
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, China; Laboratory of Transplantation and Immunology, Xuzhou Medical College, Xuzhou, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Huan-Xin
authors.initials: HX
authors.lastname: Zhang
authors.affiliation: Laboratory of Transplantation and Immunology, Xuzhou Medical College, Xuzhou, China.
authors.forename: Man
authors.initials: M
authors.lastname: Wang
authors.affiliation: Laboratory of Transplantation and Immunology, Xuzhou Medical College, Xuzhou, China.
authors.forename: Xu-Guang
authors.initials: XG
authors.lastname: Song
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, China; Laboratory of Transplantation and Immunology, Xuzhou Medical College, Xuzhou, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, China; Laboratory of Transplantation and Immunology, Xuzhou Medical College, Xuzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Laboratory of Transplantation and Immunology, Xuzhou Medical College, Xuzhou, China.
authors.forename: Jian-Lin
authors.initials: JL
authors.lastname: Qiao
authors.affiliation: Laboratory of Transplantation and Immunology, Xuzhou Medical College, Xuzhou, China.
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Lu
authors.affiliation: Department of Oncology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Zheng-Xiang
authors.initials: ZX
authors.lastname: Han
authors.affiliation: Department of Oncology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Pan
authors.affiliation: Laboratory of Transplantation and Immunology, Xuzhou Medical College, Xuzhou, China.
authors.forename: Qing-Yun
authors.initials: QY
authors.lastname: Wu
authors.affiliation: Laboratory of Transplantation and Immunology, Xuzhou Medical College, Xuzhou, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Yan
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Li
authors.affiliation: Laboratory of Transplantation and Immunology, Xuzhou Medical College, Xuzhou, China.
authors.forename: Ling-Yu
authors.initials: LY
authors.lastname: Zeng
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, China; Laboratory of Transplantation and Immunology, Xuzhou Medical College, Xuzhou, China. Electronic address: lihmd@163.com.
authors.forename: Kai-Lin
authors.initials: KL
authors.lastname: Xu
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D015820:Cadherins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects; D051176:beta Catenin / Q000096:biosynthesis*; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D000970:Antineoplastic Agents; D001549:Benzamides; D015820:Cadherins; D000068877:Imatinib Mesylate; D009363:Neoplasm Proteins; D010879:Piperazines; D011743:Pyrimidines; D051176:beta Catenin; D000099152:Cadherin 5
keywords: Imatinib; Ph+ leukemia; Stromal cells; VE-cadherin; β-Catenin