BACR 8: The role of chemerin in mediating myofibroblast effects on oesophageal squamous cancer cell (OSCC) invasion

Jothi Dinesh Kumar1,Graham J Dockray1,Andrea Varro1

1University of Liverpool, Liverpool, UK

Presenting date: Monday 2 November
Presenting time: 13.10-14.00

Background

Cancer-derived myofibroblasts (CAMs) are a key stromal cell type implicated in cancer progression. Our previous proteomic studies identified increased expression of the chemokine-like protein, chemerin, in oesophageal squamous CAMs compared with adjacent tissue myofibroblasts (ATMs). We have now studied the role of chemerin in OSCC invasion.

Method

The OSCC cell line, OE21, was studied in assays of organotypic invasion, Boyden chamber migration and invasion, and matrix metalloproteinase (MMP) activity in the presence or absence of squamous oesophageal CAMs or ATMs, or their conditioned media (CM); expression of the cognate receptor, ChemR23, was studied by immunocytochemistry.

Results

Immunocytochemistry confirmed ChemR23 expression in OE21 cells. CM from CAMs significantly increased OE21 cell migration and invasion compared with ATM CM and this was reversed by chemerin neutralizing antibody, pre-treatment with chemerin siRNA and the ChemR23 antagonist, CCX832 (generous gift from ChemoCentryx Inc). In organotypic cultures of OE21 cells on Matrigel seeded with either CAMs or ATMs, there was increased OE21 cell invasion by CAMs and this was inhibited by CCX832. Chemerin increased MMP-1, -2 and -3 abundance in OE21 cell media, and this was decreased by inhibiting protein kinase C and p44/42 MAPK kinase but not PI-3kinase.

Conclusion

Oesophageal squamous cancer myofibroblasts release chemerin which stimulates OE21 cell invasion. Treatments directed at chemerin-ChemR23 interactions might be therapeutically useful in oesophageal squamous cell cancer.