2. Academic Validation
  3. Bone Marrow Mesenchymal Stromal Cell-Derived Periostin Promotes B-ALL Progression by Modulating CCL2 in Leukemia Cells

Bone Marrow Mesenchymal Stromal Cell-Derived Periostin Promotes B-ALL Progression by Modulating CCL2 in Leukemia Cells

  • Cell Rep. 2019 Feb 5;26(6):1533-1543.e4. doi: 10.1016/j.celrep.2019.01.034.
Zhenling Ma 1,  Xueli Zhao 2,  Mingjiao Deng 2,  Zhengjie Huang 3,  Jing Wang 2,  Yi Wu 4,  Dan Cui 2,  Yingfu Liu 5,  Rushi Liu 6,  Gaoliang Ouyang 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; Cancer Research Center of Xiamen University, Xiamen, Fujian 361102, China; College of Life Sciences, Henan Agricultural University, Zhengzhou, Henan 450002, China.
  • 2 State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; Cancer Research Center of Xiamen University, Xiamen, Fujian 361102, China.
  • 3 Department of Surgical Oncology, First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, China.
  • 4 The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005, China.
  • 5 Department of Basic Medical Sciences, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
  • 6 Laboratory of Medical Molecular and Immunological Diagnostics, School of Medicine, Hunan Normal University, Changsha, Hunan 410013, China. Electronic address: [email protected].
  • 7 State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; Cancer Research Center of Xiamen University, Xiamen, Fujian 361102, China. Electronic address: [email protected].
PMID: 30726736 DOI: 10.1016/j.celrep.2019.01.034
Abstract

Periostin (POSTN) is a multifunctional extracellular component that regulates cell-matrix interactions and cell-cell crosstalk. POSTN deletion significantly decreases leukemia burden in mice; however, the underlying mechanisms by which POSTN promotes B cell acute lymphoblastic leukemia (B-ALL) progression remain largely unknown. Here, we demonstrate that bone marrow (BM)-derived mesenchymal stromal cells (BM-MSCs) express higher levels of POSTN when co-cultured with B-ALL cells in vitro and in vivo. POSTN deficiency in BM-MSCs significantly decreases CCL2 expression in co-cultured B-ALL cells in vitro and in vivo. Moreover, POSTN treatment increases expression of CCL2 in B-ALL cells by activating the integrin-ILK-NF-κB pathway. Conversely, CCL2 treatment upregulates expression of POSTN in BM-MSCs via STAT3 activation. Furthermore, there is a positive correlation between POSTN expression and CCL2 level in the BM of mice and patients with B-ALL. These findings suggest that B-ALL cell-derived CCL2 contributes to the increased leukemia burden promoted by BM-MSC-derived POSTN.

Keywords

B-ALL; CCL2; MSC; bone marrow; extracellular matrix; leukemia; matricellular protein; periostin.

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