Liver macrophages contribute to pancreatic cancer-related cachexia

Department of Surgery, Klinikum rechts der Isar, Technical University Munich, I81675 Munich, Germany.
Oncology Reports (Impact Factor: 2.3). 03/2009; 21(2):363-9. DOI: 10.3892/or_00000231
Source: PubMed


Cachexia is a devastating process especially in pancreatic cancer patients and contributes to their poor survival. We attempted to clarify the pathological and molecular changes that occur in the liver during the development of cachexia. Using immunohistochemistry we investigated the infiltration of inflammatory mononuclear cells in liver biopsies of pancreatic cancer patients with or without cachexia, and the potential relevance of the cells for the nutritional and inflammatory status. Additionally, these findings were compared with the patients' clinical parameters. We found a significantly higher amount of CD68 immunoreactive macrophages in liver cross sections of patients with pancreatic cancer and cachexia. The number of CD68-positive macrophages was significantly inversely correlated with the nutritional status. Additionally, in these CD68-positive areas a significant increase in IL-6 and IL-1 immunoreactive cells was localized. Moreover, we found significantly increased areas of CD68-positive macrophages in liver biopsies of patients with a more dedifferentiated (aggressive) grading of the tumor. In conclusion, these results suggest that a crucial interaction between the tumor, PBMCs, and the liver may play a central role in the development and regulation of cachexia. Furthermore, pancreatic cancer may be able to alter systemic organ function even without obvious metastatic disease.

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Available from: Ralf Kinscherf, Sep 16, 2014
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    • "Along these lines, hepatic TSC22D4 levels were indeed found to significantly correlate with the degree of body weight loss upon tumour development in this study. Consistent with previous reports indicating an important, as yet less appreciated, contribution of dysfunctional liver metabolism to a cachectic phenotype (Martignoni et al, 2009), these findings underline the hypothesis that specific intra-hepatic transcriptional programs significantly impact overall systemic energy availability and thereby further propagate an energy-deficient wasting condition in response to tumour burden. The TSC22 domain family of transcriptional regulators is conserved from Caenorhabditis elegans to humans and is encoded by four separate genetic loci in mammals, referred to as TSC22D1 to TSC22D4 (Gluderer et al, 2010). "
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    • "Cancer cachexia is a multifaceted syndrome characterised, among many symptoms, by marked abnormalities in lipid metabolism (Argilés et al. 1997; Barber et al. 1999). Several lines of evidence suggest that the liver plays a crucial role in the establishment and maintenance of the cachectic state (Kazantzis and Seelaender 2005; Martignoni et al. 2009). We previously demonstrated disrupted liver lipid metabolism in experimental cachexia, leading to reduced oxidation of fatty acids and decreased incorporation into very low density lipoproteins (VLDL) (Seelaender et al. 1996, 1998; Kazantzis and Seelaender 2005; Lira et al. 2008). "
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