Introduction: Cancer-associated cachexia is a metabolic syndrome characterized by weight loss and systemic inflammation. Exacerbated inflammation seems to cause protein and energy disorders leading to reduced survival and quality of life. Furthermore, systemic inflammation may be involved in muscle wasting and impaired myogenesis. Therefore, the present study aimed to evaluate satellite cells markers and cell signaling proteins in skeletal muscle of gastrointestinal cancer patients. Methods: Patients with gastrointestinal cancer were recruited after signature of the informed consent form. Rectus abdominis muscle biopsies were collected in surgery. Patients were separated into Weight-Stable Cancer (WSC) and Cachectic Cancer (CC) groups (WSC n=13 and CC n=16) according to criteria described by Evans et al (2008). Muscle mRNA was extracted and real time PCR gene expression was analysed using 2-ΔΔCT. Cell signalling proteins and CX3CL1 were quantified with Luminex®xMAP technology. Results: mRNA relative levels of two transcription factors expressed mainly by satellite cells, PAX7 and MYF5, were increased in CC patients (p=0.004 and p=0.003 respectively). Furthermore, CC muscle biopsies showed decreased JNK (p=0.006) and p53 protein content (p=0.03) and an increase in those of ATF-2 (p<0.03), cJUN (p=0.04) and mitogen- and stress-activated protein kinase (MSK1) (p=0.038) in relation to WSC patients. CX3CL1, a chemokine that may be involved in muscle regeneration, was decreased in CC patients (p=0.0004). Conclusions: Changes in satellite cells markers seems to indicate an attempt towards myoblasts proliferation and differentiation; however this process may be compromised as suggested by the lower p53 protein content. Sustained systemic inflammation may impair myocyte differentiation and consequently decrease muscle regeneration capability in CC patients. Further analysis of muscle differentiation markers are required to corroborate these findings.
Skeletal muscle dysfunction in cancer-associated cachexia characterized by changes in proliferation and differentiation markers in gastrointestinal cancer patients / Salim de Castro, Gabriela; Correia Lima Joanna Darck, Carola; Simões Fernández, Estefanía; Galvão Figueredo, Raquel; Marques de Matos-Neto, Emídio; Alcantara Martins Paulo, Sérgio; Pinhata Otoch, José; Sotiropoulos, Athanassia; Coletti, Dario; Cerqueira Leite Seelaender, Marília. - In: JOURNAL OF CACHEXIA, SARCOPENIA AND MUSCLE. - ISSN 2190-6009. - STAMPA. - (In corso di stampa). (Intervento presentato al convegno Cachexia Conference tenutosi a Rome nel 8-10 Decembre 2017).
Skeletal muscle dysfunction in cancer-associated cachexia characterized by changes in proliferation and differentiation markers in gastrointestinal cancer patients
Coletti Dario;
In corso di stampa
Abstract
Introduction: Cancer-associated cachexia is a metabolic syndrome characterized by weight loss and systemic inflammation. Exacerbated inflammation seems to cause protein and energy disorders leading to reduced survival and quality of life. Furthermore, systemic inflammation may be involved in muscle wasting and impaired myogenesis. Therefore, the present study aimed to evaluate satellite cells markers and cell signaling proteins in skeletal muscle of gastrointestinal cancer patients. Methods: Patients with gastrointestinal cancer were recruited after signature of the informed consent form. Rectus abdominis muscle biopsies were collected in surgery. Patients were separated into Weight-Stable Cancer (WSC) and Cachectic Cancer (CC) groups (WSC n=13 and CC n=16) according to criteria described by Evans et al (2008). Muscle mRNA was extracted and real time PCR gene expression was analysed using 2-ΔΔCT. Cell signalling proteins and CX3CL1 were quantified with Luminex®xMAP technology. Results: mRNA relative levels of two transcription factors expressed mainly by satellite cells, PAX7 and MYF5, were increased in CC patients (p=0.004 and p=0.003 respectively). Furthermore, CC muscle biopsies showed decreased JNK (p=0.006) and p53 protein content (p=0.03) and an increase in those of ATF-2 (p<0.03), cJUN (p=0.04) and mitogen- and stress-activated protein kinase (MSK1) (p=0.038) in relation to WSC patients. CX3CL1, a chemokine that may be involved in muscle regeneration, was decreased in CC patients (p=0.0004). Conclusions: Changes in satellite cells markers seems to indicate an attempt towards myoblasts proliferation and differentiation; however this process may be compromised as suggested by the lower p53 protein content. Sustained systemic inflammation may impair myocyte differentiation and consequently decrease muscle regeneration capability in CC patients. Further analysis of muscle differentiation markers are required to corroborate these findings.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
