Associação Portuguesa de Investigação em Cancro
Extracellular vesicles in tumor-adipose tissue crosstalk: key drivers and therapeutic targets in cancer cachexia
Extracellular vesicles in tumor-adipose tissue crosstalk: key drivers and therapeutic targets in cancer cachexia
More than half of all advanced cancer patients will experience cachexia at any point in their disease. Patients with cancer cachexia often experience unintentional weight loss mainly due to the progressive loss of body fat and skeletal muscle. This metabolic disorder severely impacts patients’ quality of life, treatments, and survival. Although nutritional supplementation is recommended in cancer cachexia patients, this solution is not capable of reversing cachexia symptoms. Therefore, a better understanding of the mechanisms underlying cancer cachexia is essential to identify important players driving this syndrome to further improve patient’s clinical outcomes.
In the last years, it has been reported the involvement of extracellular vesicles as drivers of communication between tumor cell and the adipose tissue and skeletal muscle. Extracellular vesicles are small particles released by cells to foster communication with distant cells or organs. The cargo transported by these vesicles, including miRNAs, pro-inflamatory cytokines and hormones, can induce metabolic alteration in the adipose tissue and skeletal muscle. In particular, tumor cells establish a metabolic engagement with adipose tissue, which main function is energy storage. As a feedback mechanism, mature adipocytes provide adipokines, lipids, and EVs [transporting proteins, fatty acids (FA), and lipid metabolism-related enzymes] to tumor cells, which consequently remodel their metabolism. This tumor-adipocyte crosstalk contributes for cancer progression and cachexia development.
In a review published by the international journal Extracellular Vesicles and Circulating Nucleic Acids, the researchers highlight and discuss the recent work developed in this topic. In addition, they provide valuable insights into the potential use of extracellular vesicles as emerging therapeutic targets to block or manage cancer cachexia.
Authors and Affiliations:
Cátia C. Ramos1,2,3, José Pires1,4, Esperanza Gonzalez5, Clara Garcia-Vallicrosa5, Celso A. Reis1,2,3,4, Juan M. Falcon-Perez5,6, Daniela Freitas1,2
1 i3S - Institute for Research and Innovation in Health, University of Porto, Porto 4200, Portugal.
2 IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Porto 4200, Portugal.
3 Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto 4050, Portugal.
4 Faculty of Medicine, University of Porto (FMUP), Porto 4200, Portugal.
5 Exosomes Laboratory, CIC bioGUNE-BRTA, CIBERehd, Derio 48160, Spain.
6 IKERBASQUE Research Foundation, Bilbao 48009, Spain.
Abstract:
Cancer cachexia is a complex metabolic syndrome characterized by unintentional loss of skeletal muscle and body fat. This syndrome is frequently associated with different types of cancer and negatively affects the prognosis and outcome of these patients. It involves a dynamic interplay between tumor cells and adipose tissue, where tumor-derived extracellular vesicles (EVs) play a crucial role in mediating intercellular communication. Tumor cells release EVs containing bioactive molecules such as hormones (adrenomedullin, PTHrP), pro-inflammatory cytokines (IL-6), and miRNAs (miR-1304-3p, miR-204-5p, miR-155, miR-425-3p, miR-146b-5p, miR-92a-3p), which can trigger lipolysis and induce the browning of white adipocytes contributing to a cancer cachexia phenotype. On the other hand, adipocyte-derived EVs can reprogram the metabolism of tumor cells by transporting fatty acids and enzymes involved in fatty acid oxidation, resulting in tumor growth and progression. These vesicles also carry leptin and key miRNAs (miR-155-5p, miR-10a-3p, miR-30a-3p, miR-32a/b, miR-21), thereby supporting tumor cell proliferation, metastasis formation, and therapy resistance. Understanding the intricate network underlying EV-mediated communication between tumor cells and adipocytes can provide critical insights into the mechanisms driving cancer cachexia. This review consolidates current knowledge on the crosstalk between tumor cells and adipose tissue mediated by EVs and offers valuable insights for future research. It also addresses controversial topics in the field and possible therapeutic approaches to manage cancer cachexia and ultimately improve patient outcomes and quality of life.
Journal: Extracellular Vesicles and Circulating Nucleic Acids
Link: https://www.oaepublish.com/articles/evcna.2024.36
