MC38 Tumors Induce Musculoskeletal Defects in Colorectal Cancer
| العنوان: | MC38 Tumors Induce Musculoskeletal Defects in Colorectal Cancer |
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| المؤلفون: | Fabrizio Pin, Joshua R. Huot, Andrea Bonetto, Alyson L. Essex |
| المصدر: | International Journal of Molecular Sciences Volume 22 Issue 3 International Journal of Molecular Sciences, Vol 22, Iss 1486, p 1486 (2021) |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, Colorectal cancer, Muscle Fibers, Skeletal, Gastroenterology, bone, lcsh:Chemistry, Mice, Subcutaneous Tissue, Femur, Young adult, Wasting, lcsh:QH301-705.5, Spectroscopy, Muscle Weakness, Liver Neoplasms, digestive, oral, and skin physiology, General Medicine, musculoskeletal system, Computer Science Applications, Muscular Atrophy, medicine.anatomical_structure, Disease Progression, medicine.symptom, Colorectal Neoplasms, hormones, hormone substitutes, and hormone antagonists, Muscle Contraction, STAT3 Transcription Factor, medicine.medical_specialty, colorectal cancer, Adenocarcinoma, cachexia, Article, Catalysis, Cachexia, Inorganic Chemistry, Contractility, Atrophy, Cell Line, Tumor, Internal medicine, medicine, Animals, Physical and Theoretical Chemistry, skeletal muscle, Muscle, Skeletal, Molecular Biology, neoplasms, business.industry, Organic Chemistry, Skeletal muscle, X-Ray Microtomography, medicine.disease, digestive system diseases, Blockade, Mice, Inbred C57BL, lcsh:Biology (General), lcsh:QD1-999, business, liver metastases |
| الوصف: | Colorectal cancer (CRC) is a leading cause of cancer-related death, and the prevalence of CRC in young adults is on the rise, making this a largescale clinical concern. Advanced CRC patients often present with liver metastases (LM) and an increased incidence of cachexia, i.e., musculoskeletal wasting. Despite its high incidence in CRC patients, cachexia remains an unresolved issue, and animal models for the study of CRC cachexia, in particular, metastatic CRC cachexia, remain limited therefore, we aimed to establish a new model of metastatic CRC cachexia. C57BL/6 male mice (8 weeks old) were subcutaneously (MC38) or intrasplenically injected (mMC38) with MC38 murine CRC cells to disseminate LM, while experimental controls received saline (n = 5–8/group). The growth of subcutaneous MC38 tumors was accompanied by a reduction in skeletal muscle mass (−16% quadriceps muscle), plantarflexion force (−22%) and extensor digitorum longus (EDL) contractility (−20%) compared to experimental controls. Meanwhile, the formation of MC38 LM (mMC38) led to heighted reductions in skeletal muscle mass (−30% quadriceps), plantarflexion force (−28%) and EDL contractility (−35%) compared to sham-operated controls, suggesting exacerbated cachexia associated with LM. Moreover, both MC38 and mMC38 tumor hosts demonstrated a marked loss of bone indicated by reductions in trabecular (Tb.BV/TV: −49% in MC38, and −46% in mMC38) and cortical (C.BV/TV: −12% in MC38, and −8% in mMC38) bone. Cell culture experiments revealed that MC38 tumor-derived factors directly promote myotube wasting (−18%) and STAT3 phosphorylation (+5-fold), while the pharmacologic blockade of STAT3 signaling was sufficient to preserve myotube atrophy in the presence of MC38 cells (+21%). Overall, these results reinforce the notion that the formation of LM heightens cachexia in an experimental model of CRC. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 |
| DOI: | 10.3390/ijms22031486 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fe0dd57bf24453f7ec34f115eaa54579Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fe0dd57bf24453f7ec34f115eaa54579 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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| DOI: | 10.3390/ijms22031486 |