Direct effects of delta opioid receptor agonists on invasion-associated activities of HCT-8/E11 colon cancer cells.
BACKGROUND
Opioids and opioid receptors are an integral part of the tumour microenvironment and hence may influence tumour progression. Studies on direct effects of opioids on invasion-associated cellular activities are equivocal. We wanted to clarify these differences.


METHODS
The direct effects of the delta opioid receptor (DOR) agonists [D-Pen(2), D-Pen(5)]-enkephalin (DPDPE), leu-enkephalin and [D-Ala(2), D-Leu(5)]-enkephalin (DADLE) on invasion-associated activities of HCT-8 myc-DOR and HCT-8 FLAG-DOR colon cancer cells stably overexpressing DOR were studied.


RESULTS
The opioids showed a trend to stimulate invasion of single cells in collagen in one clone, while they did not influence invasion of the other clone. In other invasion assays, no effects were observed. They did not affect cell growth and homotypical cell-cell adhesion. DPDPE at 0.1 muM inhibited directional migration; the other opioids and concentrations tested were inefficient.


CONCLUSIONS
Opioids differently influence invasion-associated cellular activities, depending on the expression level of DOR, experimental set-up, type and concentration of opioid.
Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University, De Pintelaan 185, 9000 Gent, Belgium.
Delphine
D
Debruyne
Ancy
A
Leroy
Olivier
O
DE Wever
Luc
L
Vakaet
Marc
M
Mareel
Marc
M
Bracke
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002642:Chick Embryo; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004745:Enkephalins / Q000494:pharmacology*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010766:Phosphorylation / Q000187:drug effects; D017465:Receptors, Opioid, delta / Q000819:agonists*; D018874:Spheroids, Cellular
D004745:Enkephalins; D017465:Receptors, Opioid, delta; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3