Overexpression of heme oxygenase-1 in bone marrow stromal cells promotes multiple myeloma resistance through the JAK2/STAT3 pathway.

Abstract

AIMS:

Bone marrow stromal cells (BMSCs) have been reported to interact with multiple myeloma (MM) and exert a vital function of the survival of MM cells. Heme oxygenase-1 (HO-1), a cytoprotective enzyme, has the potential to become a hematological malignancies targeted gene. This study aimed to investigate the role of HO-1 in MM resistance of BMSCs and its possible mechanisms.

MAIN METHODS:

In this study, the expression of related proteins was detected by RT-qPCR and Western blot. HO-1 expression was regulated by lentivirus transfection. Cell viability and apoptosis were detected by Flow cytometry and CCK-8. Cytokine secretion was assayed by ELISA. The survival and carcinogenic abilities was detected by clone formation assay.

KEY FINDINGS:

HO-1 expression in the BMSCs of stage III MM patients was substantially increased, compared with that of healthy donors and stage I/II patients. The results of co-culture of BMSCs and MM cells indicated that, the upregulated HO-1 inhibited the apoptosis of co-cultured MM cells, while downregulated HO-1 promoted the chemosensitivity of co-cultured MM cells, moreover, the upregulated HO-1 in BMSCs increased the colony-formation ability of MM cells. This protective capability may be regulated by CXCL12/CXCR4 signaling. High HO-1 expression in BMSCs can promote the phosphorylation of the JAK2/STAT3 pathway, thereby increasing secretion of SDF-1 in BMSCs and activating CXCL12/CXCR4 signaling. In addition, direct contact between BMSCs and MM cells may cause drug resistance.

SIGNIFICANCE:

These results indicated that the regulation of HO-1 in BMSCs may be a new effective method of MM therapy.

• Authors: Jun Huang, Lai-Quan Huang, He-Sheng He, Jiawei Yan, Chen Huang, Ran Wang, Yan Guan, Dong-Ping Huang
• Journal: Life sciences (Life Sci) Vol. 257 Pg. 118088 (Sep 15 2020) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 32663573 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• STAT3 Transcription Factor
• STAT3 protein, human
• Heme Oxygenase-1
• JAK2 protein, human
• Janus Kinase 2

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Agents (pharmacology)
• Apoptosis (genetics)
• Case-Control Studies
• Coculture Techniques
• Drug Resistance, Neoplasm
• Female
• Heme Oxygenase-1 (genetics)
• Humans
• Janus Kinase 2 (metabolism)
• Male
• Mesenchymal Stem Cells (cytology)
• Middle Aged
• Multiple Myeloma (drug therapy, genetics, pathology)
• Neoplasm Staging
• STAT3 Transcription Factor (metabolism)