Dados do Resumo

Título

Murine model of sarcoma-induced cachexia

Introdução

Cancer cachexia (CC) is a complex and systemic syndrome characterized by progressive and involuntary loss of body weight and depletion of skeletal muscle and adipose tissue. CC significantly increases the risk of morbidity and mortality, accounting for up to 40% of all cancer deaths. Although several murine models have been established to investigate CC in carcinomas, a limited number of mammalian models represents mesenchymal tumor-related cachexia, such as sarcomas.

Objetivo

To develop and characterize a new murine model of CC induced by the Sarcoma 180 (S180) tumor.

Métodos

Adult female Swiss mice weighing 25–35 g were used (CEUA/UFPI #798/2023). Animals were randomized into two groups (n = 10/group): sham (without tumor) and sarcoma (with S180). Tumor cells obtained from a donor animal with 10th day- S180 ascitic tumor, counted (32 x 10⁶ cells/0.5 mL) and inoculated i.p. into animals of the sarcoma group. All animals were kept under standard housing conditions (24 ± 1°C; 12-h light/dark cycle) with free access to water and food. Food consumption and body weight were recorded daily, locomotor activity (open field test) was assessed on the 13th day, and tumor temperature was measured by thermographic analysis on day 14. On the next day, euthanized animals were dissected out for collection of gonadal and inguinal fat, liver, heart (for histological examination), and gastrocnemius and quadriceps muscles (histomorphometric and protein analysis). Unpaired and two-tailed Student's t-test (GraphPad Prism 8.0, p < 0.05) were used for statistical analysis.

Resultados

The i.p. tumor growth rate was 100%, with an average time of 8 days for the ascitic tumor to become visible. From the 6th day after tumor induction, S180-bearing animals showed a reduction in food consumption when compared to Sham (p < 0.05), becoming more evident at the end of the protocol (Sham: 5.9g; Sarcoma: 1.8g). The behavior performance of animals with S180 tumors was worse for all parameters (crossing: 25 vs 2.7, grooming: 5 vs 1.5, rearing: 6.2 vs 0.3) and thermographic analysis showed greater heat production in tumor-bearing mice (45.6 ºC vs 50.5 ºC). The final body weight gain (Sham 4% vs Sarcoma -12%), muscle weight (0.3 vs 0.2 g/100g), total protein content (15.9 µg/mL vs 9.2 µg/mL), cross-sectional area (42000 µm2 vs 24900 µm2), and white adipose tissue content (6.5 vs 1.4 g/100g) were lower in tumor-bearing animals. All tumor-bearing animals were considered cachectic as determined by the cachexia index.

Conclusões

S180 sarcoma tumor promoted weight loss and depletion of skeletal muscle and adipose tissue, key features of CC. To date, this is the only mesenchymal tumor-derived cachexia model described in mice. The main advantages of this model are the relatively shorter time to induce CC when compared to other protocols, easy reproducibility, and the ability to study the underlying factors of mesenchymal tumor cachexia, enabling the identification of potential markers and therapeutic targets.

Financiador do resumo

CAPES (Financial code 001)

Palavras Chave

Cancer cachexia; Sarcopenia; Protein levels