Variation in dermcidin expression in a range of primary human tumours and in hypoxic/oxidatively stressed human cell lines

Abstract

Dermcidin acts as a survival factor in a variety of cancer cell lines under hypoxia or oxidative stress. The aim of this study was to evaluate dermcidin expression in cell lines following simulation of tumour microenvironmental conditions and in a range of primary tumours. Tumour tissues were collected from patients with oesophageal (28 samples), gastric (20), pancreatic (five), bile duct (one) and prostatic (52) carcinomas as well as 30 benign tissue samples, for assessment of dermcidin mRNA levels using real-time PCR. Dermcidin expression was assessed in prostatic and pancreatic cancer cell lines, with and without induction of hypoxia or oxidative stress. Dermcidin mRNA expression was very low or absent in both unstressed and stressed prostate cell lines. None of the primary prostate tissue, benign or malignant, expressed dermcidin mRNA. Only two (4%) of the gastro-oesophageal cancer samples expressed moderate quantities of dermcidin mRNA. However, three (60%) of the pancreatic cancer samples and the single cholangiocarcinoma specimen had moderate/high levels of dermcidin expression. Of the two pancreatic cancer cell lines, one expressed dermcidin moderately but neither showed a response to hypoxia or oxidative stress. Expression of dermcidin in human primary tumours appears highly variable and is not induced substantially by hypoxia/oxidative stress in cell line model systems. The relationship of these findings to dermcidin protein levels and cell survival remains to be determined.

The Multiple Facets of Dermcidin in Cell Survival and Host Defense

“…1a) [3]. Prediction analyses by FGENES or Genescan as well as expression analyses confirm the existence of only one dermcidin transcript with no splice variants [3,12,13,14,15,16]. However, one group found two alternative dermcidin splice variants with additional intronic sequences, which were found to be present in human term placenta [17].…”

“…Dermcidin expression was also found in other tumor types, such as hepatocellular carcinoma tumor tissue or cell lines [57], gastroesophageal tumors [12], pancreatic cancer cell lines [13] and in a myelogenous leukemic cell line [58]. Our own studies indicate that one can induce a low level of RNA, but not protein expression, in oxidatively stressed melanoma cells [44].…”

The appearance of dermcidin isoform 2, a novel platelet aggregating agent in the circulation in acute myocardial infarction that inhibits insulin synthesis and the restoration by acetyl salicylic acid of its effects

“…We report herein the appearance of an oxidative stress protein (OSP) in AIHD that was identified to be dermcidin isoform 2 [19] in the circulation in this condition. The role of this oxidative stress protein in the inhibition of glucose induced insulin synthesis in the islets of Langerhans as well as the effect of aspirin through the stimulation of NO synthesis in the reversal of the dermcidin induced inhibition of insulin synthesis are described in the paper.…”

Proteolysis-inducing factor core peptide mediates dermcidin-induced proliferation of hepatic cells through multiple signalling networks

“…Additionally, significantly more DCD-transfected PC-3M cells stained with Ki-67 compared with those transfected with the empty vector. Differential DCD expression has also recently been demonstrated in human pancreatic, bile duct and gastro-esophageal carcinoma but not in benign tissue (4). These studies suggest that DCD-induced proliferation could have important effects on human carcinogenesis and tumour progression.…”

“…The peptide responsible for the proliferative effects of DCD has yet to be confirmed. At least 2 of the peptides are biologically active; firstly the core peptide of proteolysis-inducing factor (PIF-CP) (3,4), which is identical to the neuronal survival factor Y-P30 (5) and when glycosylated forms the cachectic factor described by Todorov et al (6); and secondly DCD-1, which has antibiotic activity (7). Structural analysis of PIF-CP has demonstrated cleavage of a signal peptide and targeting to the secretory pathway (8).…”