Enhancing anti-tumor potential: low-intensity vibration suppresses osteosarcoma progression and augments MSCs' tumor-suppressive abilities.

Rationale: Osteosarcoma (OS), a common malignant bone tumor, calls for the investigation of novel treatment strategies. Low-intensity vibration (LIV) presents itself as a promising option, given its potential to enhance bone health and decrease cancer susceptibility. This research delves into the effects of LIV on OS cells and mesenchymal stem cells (MSCs), with a primary focus on generating induced tumor-suppressing cells (iTSCs) and tumor-suppressive conditioned medium (CM). Methods: To ascertain the influence of vibration frequency, we employed numerical simulations and conducted experiments to determine the most effective LIV conditions. Subsequently, we generated iTSCs and CM through LIV exposure and assessed the impact of CM on OS cells. We also explored the underlying mechanisms of the tumor-suppressive effects of LIV-treated MSC CM, with a specific focus on vinculin (VCL). We employed cytokine array, RNA sequencing, and Western blot techniques to investigate alterations in cytokine profiles, transcriptomes, and tumor suppressor proteins. Results: Numerical simulations validated LIV frequencies within the 10-100 Hz range. LIV induced notable morphological changes in OS cells and MSCs, confirming its dual role in inhibiting OS cell progression and promoting MSC conversion into iTSCs. Upregulated VCL expression enhanced MSC responsiveness to LIV, significantly bolstering CM's efficacy. Notably, we identified tumor suppressor proteins in LIV-treated CM, including procollagen C endopeptidase enhancer (PCOLCE), histone H4 (H4), peptidylprolyl isomerase B (PPIB), and aldolase A (ALDOA). Consistently, cytokine levels decreased significantly in LIV-treated mouse femurs, and oncogenic transcript levels were downregulated in LIV-treated OS cells. Moreover, our study demonstrated that combining LIV-treated MSC CM with chemotherapy drugs yielded additive anti-tumor effects. Conclusions: LIV effectively impeded the progression of OS cells and facilitated the transformation of MSCs into iTSCs. Notably, iTSC-derived CM demonstrated robust anti-tumor properties and the augmentation of MSC responsiveness to LIV via VCL. Furthermore, the enrichment of tumor suppressor proteins within LIV-treated MSC CM and the reduction of cytokines within LIV-treated isolated bone underscore the pivotal tumor-suppressive role of LIV within the bone tumor microenvironment.

Unlocking Glioblastoma Secrets: Natural Killer Cell Therapy against Cancer Stem Cells.

Glioblastoma (GBM) represents a paramount challenge as the most formidable primary brain tumor characterized by its rapid growth, aggressive invasiveness, and remarkable heterogeneity, collectively impeding effective therapeutic interventions. The cancer stem cells within GBM, GBM stem cells (GSCs), hold pivotal significance in fueling tumor advancement, therapeutic refractoriness, and relapse. Given their unique attributes encompassing self-renewal, multipotent differentiation potential, and intricate interplay with the tumor microenvironment, targeting GSCs emerges as a critical strategy for innovative GBM treatments. Natural killer (NK) cells, innate immune effectors recognized for their capacity to selectively detect and eliminate malignancies without the need for prior sensitization, offer substantial therapeutic potential. Harnessing the inherent capabilities of NK cells can not only directly engage tumor cells but also augment broader immune responses. Encouraging outcomes from clinical investigations underscore NK cells as a potentially effective modality for cancer therapy. Consequently, NK cell-based approaches hold promise for effectively targeting GSCs, thereby presenting an avenue to enhance treatment outcomes for GBM patients. This review outlines GBM's intricate landscape, therapeutic challenges, GSC-related dynamics, and elucidates the potential of NK cell as an immunotherapeutic strategy directed towards GSCs.