Resumen de Cross-talk in Cancer-Associated Cachexia : Dissecting systemic events of immune and endocrine system
Cancer-Associated Cachexia (CAC) is a life-threatening syndrome characterized by involuntary loss of body weight mainly due to muscle and adipose tissue wasting. It has a high incidence and frequently appears concomitant to specific tumor types, such as pancreatic or lung cancer. CAC is related to poor prognosis, complications of cancer therapy and a general impaired quality of life. Currently, this disorder is not predictable and when it occurs the available therapies are just palliative and not able to revert the progression. CAC is a multifactorial syndrome, thus, understanding the cross-talk between the tumor and the rest of the organism is essential to improve the knowledge of CAC pathophysiology and most importantly, to find biomarkers useful for cachectic patients.
Pro-inflammatory mediators are important for CAC development, and although inflammation is a feature of CAC, the role of immune cells has not been studied. Increased number of granulocytes and decreased number of lymphocytes were consistently found across 3 different mouse models of CAC. In this context diverse mouse models of neutropenia, lymphopenia and knock-outs of neutrophil-related peptides were used to investigate the contribution of immune cells in CAC. No differences were found regarding cachexia hallmarks, suggesting that alterations in the immune populations are not essential for CAC development. Interestingly, Lipocalin-2 was identified as a potential new biomarker for CAC although its role is unknown.
Appetite is frequently reduced in CAC. Neuropeptide levels were analyzed by in situ hybridization in cachectic mice and showed an activation of the orexigenic pathway. Other hormones were measured in CAC. Corticosterone levels were increased in a pre-cachectic stage. Additionally, aldosterone mRNA expression levels were significantly upregulated in CAC. Intermediate peptides from the Renin-Angiotensin-Aldosterone System (RAAS) were also altered in CAC mouse models, being potential mediators of the disease. Human sera from cancer patient cohorts were also examined, and similar changes in RAAS were observed in cachectic pancreatic and lung cancer patients compared to non-cachectic.
RAAS activation together with anemia lead to the analysis of the heart function in mouse models of CAC. Interestingly, cachectic mice showed increased left ventricle volume and altered heart function.
Altogether, these data suggest that the mechanisms leading to CAC are independent of the alteration of immune populations despite the importance of some pro-inflammatory mediators. Moreover, solid data of RAAS activation are provided, which might be linked to heart functional changes in CAC
