The expression of IL-8 and IL-8 receptors in pancreatic adenocarcinomas and pancreatic neuroendocrine tumours.
BACKGROUND
Inflammatory mediators influence tumour progression. IL-8 has been shown to have pro-angiogenic, mitogenic and motogenic effects and several studies have demonstrated the expression of IL-8 by various human pancreatic cancer cell lines.


METHODS
The expression of IL-8 and IL-8 receptors was studied in 52 pancreatic adenocarcinomas and 52 pancreatic neuroendocrine tumours using immunohistochemistry. The expression of IL-8 and IL-8 receptors was also assessed in eight pancreatic adenocarcinomas and seven neuroendocrine tumours in comparison to normal pancreatic tissue using real time quantitative PCR (qRT-PCR).


RESULTS
Immunohistochemical analysis of the expression of IL-8, IL-8RA and IL-8RB in 52 pancreatic adenocarcinomas demonstrated expression in 25%, 75% and 79% of pancreatic adenocarcinomas, respectively. There was no statistically significant correlation between expression and tumour grade and stage for any of the three antigens. IL-8, IL-8RA and IL-8RB expression was detected in 21%, 63% and 92% of 52 pancreatic neuroendocrine tumours. There was no statistically significant correlation between expression and tumour grade for any of the three antigens. Using qRT-PCR, the expression of each of IL-8, IL-8RA and IL-8RB mRNA was increased in 75% of pancreatic adenocarcinomas. IL-8, IL-8RA and IL-8RB mRNA expression was also increased in 57%, 43% and 29% of pancreatic neuroendocrine tumours. Quantitatively, there was a significant increase in expression level of IL-8 in tumours of both types in comparison to normal pancreatic tissue (38.5-fold in adenocarcinomas and 43.9-fold in neuroendocrine tumours). There was also increased expression of IL-8RA in both tumour types, with higher levels in adenocarcinomas, 2.7-fold and neuroendocrine tumours, 1.7-fold. IL-8RB was slightly increased in adenocarcinomas in comparison to normal pancreas (1.4-fold), but the expression was decreased in neuroendocrine tumours compared with normal pancreas (0.9-fold).


CONCLUSIONS
This is the first study to show that IL-8 and IL-8 receptors are upregulated in both pancreatic adenocarcinomas and neuroendocrine tumours, and indicate this signalling pathway may modulate tumour behaviour through autocrine and/or paracrine loops.
Hussain
Farah
F
Department of Surgery, Imperial College, London, UK.
Wang
Jayson
J
Ahmed
Raida
R
Guest
Stephanie K
SK
Lam
Eric W-F
EW
Stamp
Gordon
G
El-Bahrawy
Mona
M
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000473:pathology; D010179:Pancreas / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D053700:Receptors, Interleukin-8 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D055815:Young Adult
D016209:Interleukin-8; D053700:Receptors, Interleukin-8