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MMP12 knockout prevents weight and muscle loss in tumor-bearing mice

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Colorectal cancer is a malignant gastrointestinal cancer, in which some advanced patients would develop cancer cachexia (CAC). CAC is defined as a multi-factorial syndrome characterized by weight loss and muscle loss (with or without fat mass), leading to progressive dysfunction, thereby increasing morbidity and mortality | Jiang et al. BMC Cancer 2021 21 1297 https doi.org 10.1186 s12885-021-09004-y RESEARCH ARTICLE Open Access MMP12 knockout prevents weight and muscle loss in tumor-bearing mice Lingbi Jiang1 Mingming Yang1 2 Shihui He1 Zhengyang Li1 Haobin Li1 Ting Niu1 Dehuan Xie2 Yan Mei2 Xiaodong He1 Lili Wei3 Pinzhu Huang3 Mingzhe Huang3 Rongxin Zhang1 4 Lijing Wang1 and Jiangchao Li1 Abstract Background Colorectal cancer is a malignant gastrointestinal cancer in which some advanced patients would develop cancer cachexia CAC . CAC is defined as a multi-factorial syndrome characterized by weight loss and mus- cle loss with or without fat mass leading to progressive dysfunction thereby increasing morbidity and mortality. ApcMin mice develop spontaneous intestinal adenoma which provides an established model of colorectal cancer for CAC study. Upon studying the ApcMin mouse model we observed a marked decrease in weight gain beginning around week 15. Such a reduction in weight gain was rescued when ApcMin mice were crossed with MMP12 mice indicating that MMP12 has a role in age-related ApcMin -associated weight loss. As a control the weight of MMP12 mice on a weekly basis their weight were not significantly different from those of WT mice. Methods ApcMin MMP12 mice were obtained by crossing ApcMin mice with MMP12 knockout MMP12 mice. Histological scores were assessed using hematoxylin-eosin H amp E staining. MMP12 expression was confirmed by immunohistochemistry and immunofluorescence staining. ELISA protein microarrays and quantitative Polymerase Chain Reaction qPCR were used to investigate whether tumor could up-regulate IL-6. Cell-based assays and western blot were used to verify the regulatory relationship between IL-6 and MMP12. Fluorescence intensity was measured to determine whether MMP12 is associated with insulin and insulin-like growth factor 1 IGF-1 in vitro. MMP12 inhibitors were used to explore whether MMP12 could affect the body weight of ApcMin mice. Results MMP12 .