TLR3 stimulation improves the migratory potency of adipose-derived mesenchymal stem cells through the stress response pathway in the melanoma mouse model

• Published in: Molecular biology reports 2023-03, Vol.50 (3), p.2293-2304
• Main Authors: Eskandari, Fatemeh, Zolfaghari, Samira, Yazdanpanah, Ayna, Shabestari, Rima Manafi, Fomeshi, Motahareh Rajabi, Milan, Peiman B., Kiani, Jafar, Zomorrod, Mina Soufi, Safa, Majid
• Format: Article
• Language: English
• Subjects: Agonists; Animal Anatomy; Animal Biochemistry; Animals; Biomedical and Life Sciences; cancer therapy; Cellular stress response; Disease Models, Animal; genetically modified organisms; Histology; Inflammation; Integrins; Integrins - metabolism; Interleukin 10; Life Sciences; Lung cancer; lungs; Melanoma; Melanoma - metabolism; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; Mice; Mice, Inbred C57BL; migratory behavior; Morphology; Original Article; Polyinosinic:polycytidylic acid; quantitative polymerase chain reaction; Stem cells; stress response; Tissue Distribution; TLR3 protein; Toll-like receptor 3; Toll-Like Receptor 3 - metabolism; Toll-like receptors; Transforming growth factor-b; Tumors
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-022-08111-8

Background Mesenchymal stem cells (MSCs) are utilized as a carrier of anti-tumor agents in targeted anti-cancer therapy. Despite the improvements in this area, there are still some unsolved issues in determining the appropriate dose, method of administration and biodistribution of MSCs. The current study aimed to determine the influence of toll-like receptor 3 (TLR3) stimulation on the potential of MSCs migration to the neoplasm environment in the mouse melanoma model. Methods and results Adipose-derived MSCs (ADMSCs) were isolated from the GFP + transgenic C57BL/6 mouse and treated with different doses (1 µg/ml and 10 µg/ml) of polyinosinic-polycytidylic acid, the related TLR3 agonist, at various time points (1 and 4 h). Following the treatment, the expression of targeted genes such as α4, α5, and β1 integrins and TGF-β and IL-10 anti-inflammatory cytokines was determined using real-time PCR. In vivo live imaging evaluated the migration index of the intraperitoneally (IP) injected treated ADMSCs in a lung tumor-bearing mouse (C57BL/6) melanoma model (n = 5). The presented findings demonstrated that TLR3 stimulation enhanced both migration of ADMSCs to the tumor area compared with control group (n = 5) and expression of α4, α5, and β1 integrins. It was also detected that the engagement of TLR3 resulted in the anti-inflammatory behavior of the cells, which might influence the directed movement of ADMSCs. Conclusion This research identified that TLR3 activation might improve the migration via the stimulation of stress response in the cells and depending on the agonist concentration and time exposure, this activated pathway drives the migratory behavior of MSCs.