Fibroblast activation protein protects bortezomib-induced apoptosis in multiple myeloma cells through β-catenin signaling pathway
Fibroblast activation protein protects bortezomib-induced apoptosis in multiple myeloma cells through β-catenin signaling pathway
复制标题
成纤维细胞激活蛋白通过β-连环蛋白信号通路保护硼替佐米诱导的多发性骨髓瘤细胞凋亡
DOI：
10.4161/cbt.29924
复制
发表时间：
2014-07
期刊：
影响因子：
--
通讯作者：
Cai Z
中科院分区：
文献类型：
--
作者：
Han XY;Huang H;Yi Q;Cai Z
多发性骨髓瘤（MM）是一种浆细胞恶性增殖性疾病。骨髓瘤细胞与骨髓微环境的复杂交互作用在促进骨髓瘤细胞的生长和存活中起着重要作用。骨髓间充质干细胞（BMMSCs）是MM微环境中的重要细胞。在实体瘤中，BMMSC可以被肿瘤细胞训练成高表达成纤维细胞活化蛋白（FAP）的癌症相关成纤维细胞（CAF）。FAP参与肿瘤细胞的耐药性、肿瘤发生、肿瘤进展、血管生成、侵袭和转移。然而，FAP在MM骨髓微环境中的表达和作用仍然知之甚少。本研究旨在探讨FAP在硼替佐米诱导MM细胞凋亡中的表达、作用及其相关信号通路。在本研究中，我们的数据表明，FAP的表达水平之间的培养分离的骨髓间充质干细胞从MM患者和正常供体没有差异。肿瘤细胞条件培养液（TCCM）刺激或与RPMI 8226细胞共培养均可提高FAP的表达水平。FAP在BMMSCs介导的抗硼替佐米诱导的MM细胞凋亡中具有重要作用。进一步的研究表明，这一过程可能通过体外β-catenin信号通路实现。MM细胞系中β-连环蛋白的活化依赖于与BMMSC的直接接触，而不是通过transwell或额外的条件培养基与BMMSC和细胞因子分离。
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.
登录
查看更多内容
DOI：
10.1891/9780826121646.0002
发表时间：
2018-09
期刊：
Cancer Rehabilitation
影响因子：
--
作者：
K. Miller;R. Siegel;R. Khan;A. Jemal
通讯作者：
K. Miller;R. Siegel;R. Khan;A. Jemal
影响因子：
11.2
作者：
W. Rettig;P. G. Chesa;H. Beresford;Hans-Joachim Feickert;Mark T Jennings;J. Cohen;Herbert F. Oettgen;L. Old;H-J F
通讯作者：
W. Rettig;P. G. Chesa;H. Beresford;Hans-Joachim Feickert;Mark T Jennings;J. Cohen;Herbert F. Oettgen;L. Old;H-J F
影响因子：
11.2
作者：
Jonathan D. Cheng;Roland L. Dunbrack;Matthildi Valianou;A. Rogatko;R. Alpaugh;L. Weiner
通讯作者：
Jonathan D. Cheng;Roland L. Dunbrack;Matthildi Valianou;A. Rogatko;R. Alpaugh;L. Weiner
影响因子：
2
作者：
W. Shi;Juncai Liu;Man Li;Hua Gao;Ting Wang
通讯作者：
W. Shi;Juncai Liu;Man Li;Hua Gao;Ting Wang
影响因子：
4.8
作者：
Bjorklund, Chad C.;Ma, Wencai;Orlowski, Robert Z.
通讯作者：
Orlowski, Robert Z.