Myokines in treatment-naive patients with cancer-associated cachexia

Author(s):Show less -

de Castro, Gabriela S. ^{[1, 2]} ; Correia-Lima, Joanna ^{[1, 2]} ; Simoes, Estefania ^{[1, 2]} ; Orsso, Camila E. ^[3] ; Xiao, Jingjie ^{[3, 4]} ; Gama, Leonardo R. ^{[5, 6]} ; Gomes, Silvio P. ^{[1, 2, 7]} ; Goncalves, Daniela Caetano ^{[1, 2, 8]} ; Costa, Raquel G. F. ^{[1, 2]} ; Radloff, Katrin ^{[1, 2]} ; Lenz, Ulrike ^{[1, 2]} ; Taranko, Anna E. ^{[1, 2]} ; Bin, Fang Chia ^[9] ; Formiga, Fernanda B. ^[9] ; de Godoy, Louisie G. L. ^[9] ; de Souza, Rafael P. ^[10] ; Nucci, Luis H. A. ^[10] ; Feitoza, Mario ^[10] ; de Castro, Claudio C. ^{[11, 12]} ; Tokeshi, Flavio ^[12] ; Alcantara, Paulo S. M. ^[12] ; Otoch, Jose P. ^[12] ; Ramos, Alexandre F. ^{[13, 5, 6]} ; Laviano, Alessandro ^[14] ; Coletti, Dario ^{[15, 16]} ; Mazurak, Vera C. ^[3] ; Prado, Carla M. ^[3] ; Seelaender, Marilia ^{[1, 2]}

Affiliation:Show less -

^[1] Univ Sao Paulo, Canc Metab Res Grp, Inst Ciencias Biomed, Dept Biol Celular & Desenvolvimento, LIM 26-HC, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med, Dept Cirurgia, LIM 26-HC, Sao Paulo - Brazil

^[3] Univ Alberta, Dept Agr Food & Nutr Sci, Edmonton, AB - Canada

^[4] Covenant Hlth Palliat Inst, Edmonton, AB - Canada

^[5] Univ Sao Paulo, Inst Canc Estado Sao Paulo, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Dept Radiol & Oncol, Sao Paulo - Brazil

^[7] Univ Sao Paulo, Dept Cirurgia, Fac Med Vet, Sao Paulo - Brazil

^[8] Univ Fed Sao Paulo, Inst Biociencias, Santos, SP - Brazil

^[9] Santa Casa Misericoria Sao Paulo, Sao Paulo - Brazil

^[10] Inst Canc Arnaldo Vieira de Carvalho, Sao Paulo - Brazil

^[11] Univ Sao Paulo, Fac Med, Dept Radiol, Sao Paulo - Brazil

^[12] Univ Sao Paulo, Hosp Univ, Sao Paulo - Brazil

^[13] Univ Sao Paulo, Escola Artes Ciencias & Humanidades, Sao Paulo - Brazil

^[14] Sapienza Univ, Dept Translat & Precis Med, Rome - Italy

^[15] Sorbonne Univ, Dept Biol Adaptat & Aging, B2A, Rome - Italy

^[16] Sapienza Univ Rome, Dept AHFMO, Unit Histol & Med Embryol, Rome - Italy

• Document type: Journal article
• Source: Clinical Nutrition; v. 40, n. 4, p. 2443-2455, APR 2021.
• Web of Science Citations: 4

Abstract

Cancer-associated cachexia is a complex metabolic syndrome characterized by weight loss and systemic inflammation. Muscle loss and fatty infiltration into muscle are associated with poor prognosis in cancer patients. Skeletal muscle secretes myokines, factors with autocrine, paracrine and/or endocrine action, which may be modified by or play a role in cachexia. This study examined myokine content in the plasma, skeletal muscle and tumor homogenates from treatment-naive patients with gastric or colorectal stages I-IV cancer with cachexia (CC, N = 62), or not (weight stable cancer, WSC, N = 32). Myostatin, interleukin (IL) 15, follistatin-like protein 1 (FSTL-1), fatty acid binding protein 3 (FABP3), irisin and brain-derived neurotrophic factor (BDNF) protein content in samples was measured with Multiplex technology; body composition and muscle lipid infiltration were evaluated in computed tomography, and quantification of triacylglycerol (TAG) in the skeletal muscle. Cachectic patients presented lower muscle FSTL-1 expression (p = 0.047), higher FABP3 plasma content (p = 0.0301) and higher tumor tissue expression of FABP3 (p = 0.0182), IL-15 (p = 0.007) and irisin (p = 0.0110), compared to WSC. Neither muscle TAG content, nor muscle attenuation were different between weight stable and cachectic patients. Lumbar adipose tissue (AT) index, visceral AT index and subcutaneous AT index were lower in CC (p = 0.0149, p = 0.0455 and p = 0.0087, respectively), who also presented lower muscularity in the cohort (69.2% of patients; p = 0.0301), compared to WSC. The results indicate the myokine profile in skeletal muscle, plasma and tumor is impacted by cachexia. These findings show that myokines eventually affecting muscle wasting may not solely derive from the muscle itself (as the tumor also may contribute to the systemic scenario), and put forward new perspectives on cachexia treatment targeting myokines and associated receptors and pathways. (c) 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). (AU)

• FAPESP's process: 16/12508-7 - Hypothalamic changes related to the syndrome of cachexia associated with cancer: morphological analysis and histological, molecular, cellular and systemic central nervous system study
• Grantee: Estefania Simoes Fernandez
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 12/50079-0 - Systemic inflammation in cachectic cancer patients: mechanisms and therapeutical strategies, a translational medicine approach
• Grantee: Marilia Cerqueira Leite Seelaender
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/13810-9 - Cachexia associated with cancer and lipid metabolism: can chronic exercise affect fatty acids location and profile in muscle?
• Grantee: Gabriela Salim Ferreira de Castro
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/25207-7 - Is inflammation resolution failing in adipose tissue of cachectic patients?
• Grantee: Katrin Radloff
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 16/02780-1 - Molecular analysis in the tumor microenvironment of cachectic patients: A search of markers for early diagnosis of the syndrome
• Grantee: Joanna Darck Carola Correia Lima
• Support Opportunities: Scholarships in Brazil - Doctorate