Molecular and Physiological Evaluation of Pancreatic Cancer-Induced Cachexia

Methods Mol Biol. 2019:1882:321-333. doi: 10.1007/978-1-4939-8879-2_28.

Abstract

Cachexia, a complex metabolic syndrome, is characterized by involuntary weight loss along with muscle wasting and fat depletion leading to poor quality of life of patients. About 80% of pancreatic cancer patients exhibit cachectic phenotype at the time of diagnosis. Here, we present the several molecular and physiological parameters, which we utilize to study the pancreatic cancer-induced cachexia in in vitro models and preclinical mice models of pancreatic cancer. We have described myotube and adipocyte-based in vitro models of muscle and fat wasting, including methods of cell culture, differentiation, and treatment with cancer cell-conditioned medium. Furthermore, we have explained the methods of evaluation of key cachectic markers for muscles. Next, we have detailed the orthotopic implantation mouse models of pancreatic cancer and evaluation of different physiological parameters, including body weight, food intake, body composition analysis, glucose tolerance test, insulin resistance test, grip strength measurement, and rotarod performance test. We have also explained morphological parameters and molecular markers to evaluate the muscle wasting in pancreatic cancer-induced cachexia.

Keywords: 3T3L1; C2C12; Cachexia; Fat depletion; Muscle wasting; Orthotopic implantation model; Pancreatic cancer.

MeSH terms

  • 3T3-L1 Cells
  • Absorptiometry, Photon
  • Adipocytes / physiology
  • Animals
  • Cachexia / diagnosis
  • Cachexia / etiology
  • Cachexia / pathology*
  • Cachexia / physiopathology
  • Cell Culture Techniques / instrumentation
  • Cell Culture Techniques / methods*
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Culture Media, Conditioned / pharmacology
  • Disease Models, Animal
  • Humans
  • Mice
  • Mice, Nude
  • Muscle Fibers, Skeletal / physiology
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Pancreatic Neoplasms / complications*
  • Pancreatic Neoplasms / pathology
  • Rotarod Performance Test / instrumentation
  • Rotarod Performance Test / methods
  • Xenograft Model Antitumor Assays / instrumentation
  • Xenograft Model Antitumor Assays / methods*

Substances

  • Culture Media, Conditioned