Fibroblast activation protein protects bortezomib-induced apoptosis in multiple myeloma cells through β-catenin signaling pathway

Fu Ming Zi, Jing Song He, Yi Li, Cai Wu, Wen Jun Wu, Yang Yang, Li Juan Wang, Dong Hua He, Li Yang, Yi Zhao, Gao Feng Zheng, Xiao Yan Han, He Huang, Qing Yi, Zhen Cai

Research output: Contribution to journalArticle

14 Scopus citations

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 bort-ezomib. 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.

Original languageEnglish (US)
Pages (from-to)1413-1422
Number of pages10
JournalCancer Biology and Therapy
Volume15
Issue number10
DOIs
StatePublished - Oct 1 2014

Keywords

  • Apoptosis
  • Bone marrow mesenchymal stem cells
  • Cancer-associated fibroblast
  • Fibroblast activation protein
  • Multiple myeloma
  • Signaling pathway
  • β-catenin

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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