Hypoxia-driven mobilization of altruistic cancer stem cells in platinum-treated head and neck cancer

• DOI: 10.3389/fimmu.2024.1336882
• Publication Date: 2025-02-03T06:36:29Z
• Authors: Lekhika Pathak; Bidisha Pal; Joyeeta Talukdar; Partha Jyoti Saikia; Sorra Sandhya; Wale Tasabehji; Hong Li; Jyotirmoy Phukan; Anjan Bhuyan; Sanjukta Patra; Bikul Das
• Keywords: Circulating tumor cell; Hypoxia

Background Head and neck cancers harbor dormant cancer stem cells (CSCs). This study explores how platinum therapy impacts these in a non-genetic manner the role of hypoxia this process. Previously, we identified novel population CSCs exhibiting an “altruistic” phenotype, sacrificing self-renewal to promote niche defense (tumor stemness defense, TSD), potentially protecting subpopulation CSCs, reawakening CSC (R-CSC) retaining stress memory. TSD phenotype involves activation MYC-HIF2α pathway and, importantly, is linked hypoxic tumor microenvironment. We termed TSD+ “altruistic cells” (A-CSCs). Here investigated potential mobilization circulation as part against therapy. Methods isolated CTCs primary from head squamous cell carcinoma (HNSCC) patients undergoing ( n = 14). analyzed markers cells. Additionally, further characterized previously reported pre-clinical model platinum-induced link between hypoxia, emergence, bone marrow. Results with signature eight out 14 HNSCC patients. These displayed increased proliferation invasion upon cisplatin treatment, suggesting defense. Our confirmed that directly correlates expansion their into marrow following treatment. demonstrated protection R-CSCs by CSCs. Notably, inhibiting alone tirapazamine did not reduce CTCs, or R-CSCs. However, combining FM19G11, inhibitor, significantly reduced both presence Conclusions reveals can altruistic signature. provides mechanism resistance-the self-defense. The microenvironment, through emergence appears act collectively defend self-identity hijacking mechanism.