Caspase-1/11 deficiency and cold exposure enhance the anti-tumor activity of brown adipose tissue secretome against breast cancer cells

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

BACKGROUND: Adipose tissue metabolic plasticity and inflammation critically influence tumor progression through endocrine signaling. While white adipose tissue (WAT) has been linked to pro-tumorigenic effects in obesity-related cancers, the influence of brown adipose tissue (BAT) and its secretome on breast cancer remains incompletely understood. Furthermore, how caspase-1/11–mediated inflammasome signaling regulates adipose tissue endocrine function in this context is largely unexplored. This study investigated the differential effects of WAT and BAT secretomes on breast cancer aggressiveness and elucidate the impact of caspase-1/11 deficiency on adipose tissue-tumor crosstalk. METHODS: Conditioned media (CM) were generated from WAT and BAT of wild-type (WT) and caspase-1/11 knockout (KO) C57BL/6 mice, including animals subjected to cold-induced BAT activation. 4T1 breast cancer cells were exposed to these secretomes, and carcinogenic parameters were assessed, including viability (MTT), cell death (Annexin-V/PI), proliferation (CFSE), migration (wound healing assay), lipid droplet biogenesis (BODIPY and Oil Red staining and microscopy), oxidative stress (ROS and nitrite quantification), and cytokine production (ELISA). Additionally, splenocytes were also stimulated with the secretomes to assess their effect on T and NKT cell activation (Flow cytometry). Global proteomic profil

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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