Conditioned Media from Head and Neck Cancer Cell Lines and Serum Samples from Head and Neck Cancer Patients Drive Catabolic Pathways in Cultured Muscle Cells
by
, , , and
Nicolas Saroul
1,2,3,*, 
Nicolas Tardif
4,5,
Bruno Pereira
3
,
Alexis Dissard
1,2,
Laura Montrieul
1,2,
Phelipe Sanchez
2,
Jérôme Salles
2,
Jens Erik Petersen
1,2,
Towe Jakobson
4,
Laurent Gilain
1,
Thierry Mom
1
,
Yves Boirie
2,6,
Olav Rooyakers
4,5 and
Stéphane Walrand
2,6 1
Otolaryngology Head and Neck Surgery Department, CHU de Clermont-Ferrand France, 63000 Clermont-Ferrand, France
2
Human Nutrition Unit, INRAE, Auvergne Human Nutrition Research Center, Clermont Auvergne University, CHU de Clermont-Ferrand France, INRAE, UNH, 63000 Clermont-Ferrand, France
3
Biostatistics Department, CHU de Clermont-Ferrand France, 63000 Clermont-Ferrand, France
4
Anesthesiology and Intensive Care, Department of Clinical Science Intervention and Technology, CLINTEC, Karolinska Institutet, 141 86 Huddinge, Sweden
5
Division of Perioperative Medicine and Intensive Care, Karolinska University Hospital, 171 77 Huddinge, Sweden
6
Clinical Nutrition Department, CHU de Clermont-Ferrand France, 63000 Clermont-Ferrand, France
*
Author to whom correspondence should be addressed.
Cancers 2023, 15(6), 1843; https://doi.org/10.3390/cancers15061843
Submission received: 26 January 2023
/
Revised: 10 March 2023
/
Accepted: 13 March 2023
/
Published: 19 March 2023
(This article belongs to the Section Cancer Pathophysiology)
Simple Summary
Cancer cachexia in head and neck cancer (HNC) is mainly due to a decrease in food intake, but other causal mechanisms could also be involved. The role of secreted factors from the tumor cells in driving cancer cachexia and especially muscle loss is unknown. In this way, we wanted to study both the action of secreted factors from HNC cell lines and circulating factors in HNC patients on skeletal muscle protein catabolism. We used a conditioned media model and mix of sera from cancer patients to analyze the in vitro metabolic response with primary myotubes. The same metabolic response was obtained with tumor-conditioned media and mix of sera from cancer patients. Patient plasma compounds produced specifically by the tumor seemed to have this effect. Our results indicated that the atrophy observed in HNC patients cannot be solely explained by a deficit in food intake.
Abstract
Background: The role of secreted factors from the tumor cells in driving cancer cachexia and especially muscle loss is unknown. We wanted to study both the action of secreted factors from head and neck cancer (HNC) cell lines and circulating factors in HNC patients on skeletal muscle protein catabolism. Methods: Conditioned media (CM) made from head and neck cancer cell lines and mix of sera from head and neck cancer (HNC) patients were incubated for 48 h with human myotubes. The atrophy and the catabolic pathway were monitored in myotubes. The patients were classified regarding their skeletal muscle loss observed at the outset of management. Results: Tumor CM (TCM) was able to produce atrophy on myotubes as compared with control CM (CCM). However, a mix of sera from HNC patients was not able to produce atrophy in myotubes. Despite this discrepancy on atrophy, we observed a similar regulation of the catabolic pathways by the tumor-conditioned media and mix of sera from cancer patients. The catabolic response after incubation with the mix of sera seemed to depend on the muscle loss seen in patients. Conclusion: This study found evidence that the atrophy observed in HNC patients cannot be solely explained by a deficit in food intake.
