title: Bone marrow mesenchymal stem cells regulate stemness of multiple myeloma cell lines via BTK signaling pathway.
abstract: Bone marrow mesenchymal stem cells (BM-MSCs) are key components of bone marrow microenvironment. Although the importances of BM-MSCs activation in myeloma cells growth, development, progression, angiogenesis are well known, their role in the regulation of myeloma stemness is unclear. In this study, myeloma cell lines (LP-1, U266) were co-cultured with BM-MSCs, we found that BM-MSCs could up-regulate the expression of key stemness genes and proteins (OCT4, SOX2, NANOG) and increase clonogenicity. Similarly, the mechanisms underlying the BM-MSC activation of myeloma stemness remain unclear. Here, we found that PCI-32765, a Bruton tyrosine kinase (BTK) inhibitor, treatment significantly down- regulate expression of key stemness genes and proteins in vitro co-culture system. Together, our results revealed that BM-MSCs could increase myeloma stemness via activation of the BTK signal pathway.
authors.affiliation: Department of Hematology and Blood and Marrow Transplantation, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of Hematology and Blood and Marrow Transplantation, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Yafang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Hematology and Blood and Marrow Transplantation, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Yue
authors.affiliation: Department of Hematology and Blood and Marrow Transplantation, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Hematology and Blood and Marrow Transplantation, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China. Electronic address: xiaofangwang1@126.com.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Wang
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D001854:Bone Marrow Cells / Q000166:cytology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D000071317:Nanog Homeobox Protein / Q000235:genetics; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000235:genetics; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human
keywords: Bone marrow mesenchymal stem cells; Bruton tyrosine kinase; Multiple myeloma; PCI-32765; Stemness