Thus, HOPX may therefore affect critical process of chromatin selleck chem conformation change to affect expression of onco molecules. Collectively, we found that HOPX methylation is a very frequent and cancer specific event in PC develop ment. We further elucidated that HOPX is a putative tumor suppressor gene critical for tumor aggressiveness in PC. We are also interested in alternate aspects of HOPX in terms of a role in islet cells. We must confirm more detailed mechanism involved in remarkable phenotype alteration by HOPX abnormalities in PC in future study. Conclusions Defective expression of HOPX which is consistent with CpG islands promoter DNA hypermethylation may explain aggressive phenotype of pancreatic cancer, and intense ex pression of HOPX in the Langerhans islet cells may in turn uniquely contribute to pancreatic carcinogenesis.
Background Interleukin 6 is a four helical protein of 184 amino acids that belongs to a large family of pleiotropic cytokine involved in numerous functions. On target cells, IL 6 binds to an 80 kDa IL 6 receptor. The complex of IL 6 and IL 6R couples with gp130 protein and triggers intracellular signaling. Whereas gp130 is expressed on all cells, IL 6R is only present on few cells in the body including hepatocytes and some leukocytes. Cells not expressing IL 6R cannot respond to the cytokine, since gp130 alone has no measurable affinity for IL 6. A soluble form of IL 6R comprising the extra cellular portion of the receptor can bind IL 6 with a similar affinity as the membrane bound IL 6R.
The complex of IL 6 and sIL 6R can bind to gp130 on cells, which do not express the IL 6R, and which are unre sponsive to IL 6. This alternative stimulation has been called trans signaling. There is evidence that IL 6 trans signaling possess a prevalent pro inflammatory role, whereas classic IL 6 signaling via the membrane bound IL 6R is needed for regenerative or anti inflammatory processes. Dysregulation of the IL 6/IL 6R system has been associ ated with the pathogenesis of several autoimmune and in flammatory diseases in humans, and anti IL 6 monoclonal antibodies have been successfully developed for the medical treatment of chronic inflammatory diseases, like rheumatoid arthritis. Recently, anti IL 6 moAbs have drawn attention for their potential effects in can cer patients. On one side, IL 6 and other pro inflammatory cytokines are involved in the mechanisms that promote cancer cachexia. Also, there is evidence that IL 6 directly induces tumor growth and spread after triggering the canonical JAK/STAT pathway, an SHP 2 driven Ras Raf MAPK signaling pathway Dacomitinib and angiogenesis. Activation of these pathways has been documented in gastric cancer in experimental models and in vivo.