Introduction Metabolic reprogramming is a hallmark of cancer cells that promotes tumor initiation and progression, with mitochondrial function as a key determinant. Profound evidence is pointing to a detrimental influence of tumors on the surrounding tissue, but also tumor-induced systemic metabolic alterations are increasingly unraveled. In this way, blood cells can be affected. We thus, asked whether mitochondrial alterations can be assessed in cancer patient platelets as they serve as major mitochondria reservoir in blood.

Material and methods We established a protocol to measure mitochondrial respiration of isolated permeabilized platelets with high-resolution respirometry (Oroboros Instruments). The study enrolled 15 head and neck squamous cell carcinoma (HNSCC) patients and 15 healthy donors. Further electron microscopy imaging was used to analyze platelet morphology. RNA-sequencing data of platelet isolates completed the analysis of mitochondrial deficits.

Results RNA-sequencing of platelets from HNSCC patients indicated mitochondrial functional alterations. While platelet mitochondrial structures appeared similar, high-resolution respirometry revealed a reduced electron transfer capacity in platelet mitochondria from HNSCC patients compared to healthy donors.

Conclusion We find reduced respiratory chain function and impaired oxidative phosphorylation of platelet mitochondria in HNSCC patients. Clearly, metabolic alterations in the blood residing platelets add to implement a systemic ketogenic phenotype in such cancers. This could therefore not only become an important diagnostic tool to detect mitochondria-linked diseases but also plausibly provide a basis for new therapeutic approaches concerning tumor initiation and progression.

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