title: Fibroblast activation protein protects bortezomib-induced apoptosis in multiple myeloma cells through β-catenin signaling pathway.
abstract: Multiple myeloma (MM) is a malignant plasma cells proliferative disease. The intricate cross-talk of myeloma cells with bone marrow microenvironment plays an important role in facilitating growth and survival of myeloma cells. Bone marrow mesenchymal stem cells (BMMSCs) are important cells in MM microenvironment. In solid tumors, BMMSCs can be educated by tumor cells to become cancer-associated fibroblasts (CAFs) with high expression of fibroblast activation protein (FAP). FAP was reported to be involved in drug resistance, tumorigenesis, neoplastic progression, angiogenesis, invasion, and metastasis of tumor cells. However, the expression and the role of FAP in MM bone marrow microenvironment are still less known. The present study is aimed to investigate the expression of FAP, the role of FAP, and its relevant signaling pathway in regulating apoptosis induced by bortezomib in MM cells. In this study, our data illustrated that the expression levels of FAP were not different between the cultured BMMSCs isolated from MM patients and normal donors. The expression levels of FAP can be increased by tumor cells conditioned medium (TCCM) stimulation or coculture with RPMI8226 cells. FAP has important role in BMMSCs mediated protecting MM cell lines from apoptosis induced by bortezomib. Further study showed that this process may likely through β-catenin signaling pathway in vitro. The activation of β-catenin in MM cell lines was dependent on direct contact with BMMSCs other than separated by transwell or additional condition medium from BMMSCs and cytokines.
authors.affiliation: Bone Marrow Transplantation Center; The First Affiliated Hospital; Zhejiang University School of Medicine; Hangzhou, PR China.
authors.forename: Fu-Ming
authors.initials: FM
authors.lastname: Zi
authors.affiliation: Bone Marrow Transplantation Center; The First Affiliated Hospital; Zhejiang University School of Medicine; Hangzhou, PR China.
authors.forename: Jing-Song
authors.initials: JS
authors.lastname: He
authors.affiliation: Bone Marrow Transplantation Center; The First Affiliated Hospital; Zhejiang University School of Medicine; Hangzhou, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Bone Marrow Transplantation Center; The First Affiliated Hospital; Zhejiang University School of Medicine; Hangzhou, PR China.
authors.forename: Cai
authors.initials: C
authors.lastname: Wu
authors.affiliation: Bone Marrow Transplantation Center; The First Affiliated Hospital; Zhejiang University School of Medicine; Hangzhou, PR China.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Wu
authors.affiliation: Bone Marrow Transplantation Center; The First Affiliated Hospital; Zhejiang University School of Medicine; Hangzhou, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Bone Marrow Transplantation Center; The First Affiliated Hospital; Zhejiang University School of Medicine; Hangzhou, PR China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Wang
authors.affiliation: Bone Marrow Transplantation Center; The First Affiliated Hospital; Zhejiang University School of Medicine; Hangzhou, PR China.
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: He
authors.affiliation: Bone Marrow Transplantation Center; The First Affiliated Hospital; Zhejiang University School of Medicine; Hangzhou, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Bone Marrow Transplantation Center; The First Affiliated Hospital; Zhejiang University School of Medicine; Hangzhou, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Bone Marrow Transplantation Center; The First Affiliated Hospital; Zhejiang University School of Medicine; Hangzhou, PR China.
authors.forename: Gao-Feng
authors.initials: GF
authors.lastname: Zheng
authors.affiliation: Bone Marrow Transplantation Center; The First Affiliated Hospital; Zhejiang University School of Medicine; Hangzhou, PR China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Han
authors.affiliation: Bone Marrow Transplantation Center; The First Affiliated Hospital; Zhejiang University School of Medicine; Hangzhou, PR China.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Cancer Biology; Lerner Research Institute; Cleveland Clinic; Cleveland, OH USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yi
authors.affiliation: Bone Marrow Transplantation Center; The First Affiliated Hospital; Zhejiang University School of Medicine; Hangzhou, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cai
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000378:metabolism; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D010450:Endopeptidases; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D009101:Multiple Myeloma / Q000473:pathology*; D011719:Pyrazines / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism*; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D000069286:Bortezomib; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D011719:Pyrazines; D012697:Serine Endopeptidases; D051176:beta Catenin; D000099167:Fibroblast Activation Protein Alpha
keywords: apoptosis; bone marrow mesenchymal stem cells; cancer-associated fibroblast; fibroblast activation protein; multiple myeloma; signaling pathway; β-catenin