Globular adiponectin, acting via adiponectin receptor-1, inhibits leptin-stimulated oesophageal adenocarcinoma cell proliferation

Abstract

Obesity increases the risk of developing several cancers including oesophageal adenocarcinoma (OAC). Obesity is characterized by hyperleptinaemia and hypoadiponectinaemia: we have hypothesized that these hormonal factors may contribute to the progression of OAC. We have examined the effects of leptin and adiponectin on proliferation of OAC cells. Leptin stimulated proliferation in 4 different OAC lines (OE33, OE19, BIC-1 and FLO) and this was inhibited by globular but not full length adiponectin. All 4 OAC lines expressed both adiponectin-receptor isoforms (AdipoR1 and AdipoR2).

Inhibition of smooth muscle cell proliferation by adiponectin requires proteolytic conversion to its globular form

“…Additionally, adiponectin had no effect on the proliferation of normal and transformed breast cancer cells and adenocarcinomas (Grossmann et al 2008, Ogunwobi & Beales 2008. Similar results have been obtained with globular adiponectin, with i) growth of epithelial cancer cells, fibroblasts, and hematopoietic stem cells increased (Ogunwobi & Beales 2006, DiMascio et al 2007, Hattori et al 2007; ii) epithelial and breast cancer cells and adenocarcinomas growth inhibited (Fenton et al 2008, Grossmann et al 2008, Ogunwobi & Beales 2008; and iii) growth of normal breast cells and prostate cancer cells unaffected (Grossmann et al 2008, Mistry et al 2008. In studies that directly compared the two forms of adiponectin, both different (breast, prostate, and adenocarcinoma) and similar (epithelial and stem cells) responses have been observed.…”

“…For instance, adiponectin has been reported to inhibit the proliferation of hepatic stellate and breast cancer cells (Adachi & Brenner 2008, Nakayama et al 2008 and promote the proliferation of epithelial, breast, and prostate cancer cells, as well as osteoblasts and hematopoietic stem cells (Luo et al 2006, Ogunwobi & Beales 2006, DiMascio et al 2007, Mistry et al 2008, Pfeiler et al 2008. Additionally, adiponectin had no effect on the proliferation of normal and transformed breast cancer cells and adenocarcinomas (Grossmann et al 2008, Ogunwobi & Beales 2008. Similar results have been obtained with globular adiponectin, with i) growth of epithelial cancer cells, fibroblasts, and hematopoietic stem cells increased (Ogunwobi & Beales 2006, DiMascio et al 2007, Hattori et al 2007; ii) epithelial and breast cancer cells and adenocarcinomas growth inhibited (Fenton et al 2008, Grossmann et al 2008, Ogunwobi & Beales 2008; and iii) growth of normal breast cells and prostate cancer cells unaffected (Grossmann et al 2008, Mistry et al 2008.…”

Leptin prevents the metabolic effects of adiponectin in L6 myotubes

“…Leptin is known to regulate a wide range of intracellular signalling pathways [21]; however the potential crosstalk between leptin and adiponectin signalling is unclear. To date, three recent studies examining cell cycle regulation and cell proliferation have demonstrated that adiponectin and leptin can crosstalk [22][23][24]. The objective of this study was to characterise the effect of chronic leptin pretreatment on subsequent adiponectin signalling and consequently on metabolic function in rat skeletal muscle cells.…”

Reduced Risk of Barrett’s Esophagus in Statin Users: Case–Control Study and Meta-Analysis

“…Thus it is possible that statin and aspirin impair survival of the Barrett's clone at a very early stage and so impair establishment of a mature Barrett's segment. There are several putative mechanisms that could also be involved: aspirin reduced NF-kB signalling (38), which may in turn alter the nuclear transcription factor milieu that seems to be important in driving the development of Barrett's (39) and statins may influence the secretion of adipokines (such as adiponectin and leptin) which in term seem to influence the behaviour of metaplastic Barrett's epithelial cells (40)(41)(42)(43)(44)). …”