• Growth factors
• biliary duct carcinoma
• IL-6
• cholangiocarcinoma
• fatty liver
• cholestatic liver diseases
• bile secretion
• intracellular signalling

Cholangiocarcinoma (CCA) is a cancer that may develop in any portion of the biliary tree and is characterised by a bad prognosis and virtually no response to chemotherapy.1 2 In Western countries the incidence of intrahepatic CCA is progressively growing while that of extrahepatic CCA is stable or slightly decreasing.3 A number of recent studies have investigated the agents and mechanisms modulating the proliferation of CCA cells including growth factors, cytokines, neuropeptides and hormones.4 In their paper published in this issue of Gut, Frampton et al5 provide compelling evidence that progranulin (PGRN) represents a new growth factor for CCA. The expression and secretion of PGRN is upregulated in CCA cell lines and human CCA biopsies, and this is in part occurs via interleukin 6 (IL-6)-mediated activation of the ERK1/2/RSK1/C/EBPβ pathway. Knockdown of PGRN expression in CCA cells decreased the expression of proliferating cellular nuclear antigen, a marker of cell proliferation, and slowed tumour growth in vivo. The authors suggest that PGRN may be a potential target for the development of novel therapeutic strategies for CCA.5

PGRN is a secreted glycoprotein consisting of tandem repeats of a 12-cysteine module called granulin or epithelin domain. It is proteolytically degraded by elastase with the release of 6 kDa peptides corresponding to …