Some non-muscular tissues and organs –even tumours- can synthetize molecules that alter metabolic regulation pathways in those affected by cachexia, a cancer-associated pathology –among other illnesses- which is presented by a severe reduction of the adipose tissue and muscle mass.
Molecular signals that regulate the communication between corporal tissues in oncological cachexia cases are now detailed in a review published by the journal Nature Reviews in Endocrinology, signed by the experts Josep M. Argilés, Sílvia Busquets and Francisco J. López Soriano, from the Department of Biochemistry and Molecular Biomedicine and the Institute of Biomedicine (IBUB) of the UB, and Britta Stemmler (BS Nutrition Centre).
Cancer Cachexia: molecular signals
Cachexia is a multi-organ syndrome present in several pathologies (cancer, chronic infections, etc.). Several tumoral factors –for instance, PIF, LMF, and PTHrP- and other molecules –cytokine like IL-6- are the main biochemical mediators in communication pathways between tissues in cancer cachexia, according to the experts of the UB, members of the Research Group of Biochemistry and Molecular Biology of Cancer.
Regarding the tumours, cancer cells do not respond to molecular signals in their environment and show a deeply altered energetic metabolism. The high demand of energy of these tissues –competing with the rest of the cells for nutrients- and less intake of food from the affected ones determine the progress of the pathology. Cachexia, as a whole, reduces the effectiveness of anti-tumour treatments, damages the life quality of the patient and worsens the evolution of the tumour case.
Molecular connections between inflammatory processes, metabolism and cancer are also reviewed in the new study, which highlights the role of the systemic inflammation in the activation of the muscle mass loss. In particular, the systemic inflammation –which affects the whole body- is a process that can unchain a multi-organ response that alters the protein metabolism in the liver and activates the synthesis of acute-phase proteins.
A dual action path for the adipose tissue
Interestingly, the metabolic role of the adipose tissue in the cases of cancer cachexia has not properly described in the scientific bibliography. According to the authors, the adipose tissue (white and brown) plays an active metabolic role, and it’s dual: on the one hand, it boosts the release of molecular signals to the skeletal muscle to shape the protein replacement, on the other, it activates thermogenesis –through the transformation of white adipose cells into brown ones-, so that it creates metabolic inefficiency and contributes to the patients’ weight loss.
Treating cachexia in oncological patients requires the participation of multi-disciplinary teams (oncologists, nutritionists, dieticians, dentists, psychologists) to work from broad perspectives on the illness (drugs, nutritional advice, physical activity, etc.). The team of experts of the UB, leader in the international scenario of research on cachexia, notes it is essential to improve the general state of the patient –regarding the intake and tumour-induced metabolic changes- to benefit the efficiency of the anti-tumour treatment and prognosis of each patient illness.
Universitat de Barcelona