Microvesicles of osteoblasts modulate bone marrow mesenchymal stem cell‐induced apoptosis to curcumin in myeloid leukemia cells

• Published in: Journal of cellular physiology 2019-10, Vol.234 (10), p.18707-18719
• Main Authors: Zahedpanah, Mahdi, Takanlu, Javid Sabour, Nikbakht, Mohsen, Rad, Fariba, Farhid, Fatemeh, Mousavi, Seyed Asadollah, Rad, Soroush, Fumani, Hosein Kamranzadeh, Hosseini Rad, Seyed Mohammad Ali, Mohammadi, Saeed
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - drug effects; Biocompatibility; Bone marrow; Cell adhesion; Cell adhesion & migration; Cell adhesion molecules; Cell Communication - drug effects; Cell Line, Tumor; Cell Survival - drug effects; Cell-Derived Microparticles - metabolism; Cell-Derived Microparticles - ultrastructure; chemoresistance; Curcumin; Curcumin - pharmacology; Daunorubicin; Down-Regulation - drug effects; Drugs; Dynamic Light Scattering; Gene expression; Gene Expression Regulation, Leukemic - drug effects; Humans; Information transfer; Interleukins; Leukemia; Leukemia, Myeloid - genetics; Leukemia, Myeloid - pathology; Mesenchymal Stem Cells - cytology; Mesenchyme; microvesicles; Myeloid leukemia; niche cells; Osteoblasts; Osteoblasts - drug effects; Osteoblasts - metabolism; Osteopontin; Stat3 protein; Stem cells; Survival; Vascular cell adhesion molecule 1
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.28511

Microvesicles (MVs) derived from bone marrow niche components have an important role in genetic reprogramming and subsequent drugs induce apoptosis in leukemic cells. Here, we have found that undertreatment of curcumin or daunorubicin, the cross‐talk through MVs of KG‐1‐bone marrow mesenchymal stem cells (BMSCs), significantly downregulates the expression of the survival gene osteopontin (OPN), CXCL‐12, IL‐6 (interleukin‐6), STAT‐3, and VCAM‐1 (vascular cell adhesion molecule 1) in treated‐KG‐1 cells as well as exclusively upregulates CXCL‐12 in BMSCs. Drug treated‐cell populations’ MVs of both single cultured osteoblasts (OBs) and cocultured KG‐1 + BMSCs + OBs similarly upregulate survival mediators’ OPN, CXCL‐12, IL‐6, STAT‐3, and VCAM‐1 in treated‐KG‐1 cells. Likewise, isolated MVs from KG‐1 cells or communication between KG‐1, BMSCs, and OBs treated by drugs increase the expression of genes OPN, CXCL‐12, IL‐6, STAT3, and VCAM‐1 by OBs. MVs derived from KG‐1 + BMSCs + OBs reduce drug‐induced apoptosis in KG‐1 cells. This suggests MVs‐mediated information transfer is a procedure whereby OBs could overcome BMSCs‐induced apoptosis in drug‐treated‐KG‐1 cells.