DPPIV inhibitors extend GLP-2 mediated tumour promoting effects on intestinal cancer cells.
BACKGROUND
The glucagon-like peptides-1 and -2 (GLP-1 and -2) are co-secreted after food intake from intestinal L cells. Since both peptides are rapidly degraded by dipeptidyl peptidase-IV (DPPIV), research is focused on the development of DPPIV inhibitors or DPPIV resistant.


OBJECTIVE
In this study we investigated, whether the inhibition of DPPIV activity and the resulting increased half-life of DPPIV substrates may influence cancer development and progression.


METHODS
We examined proliferation and migratory activity of two human colon cancer cell lines (SW480, HT29) after stimulation with GLP-2 in combination with or without DPPIV inhibitors.


RESULTS
Migratory activity was increased by 25% from 20% matrix induced activity to a maximum of 45% (100 nM GLP-2). In cells expressing CD26, migration was prolonged by addition of DPPIV inhibitors in a concentration dependent manner. After treatment with GLP-2 doubling time decreased from 2.4 to 1.5 days - and addition of DPPIV inhibitors enhanced the effect of GLP-2.


CONCLUSIONS
The use of DPPIV inhibitors together with GLP-2 led to increased proliferation as well as elevated migratory activity. Therefore, the use of DPPIV inhibitors could increase the risk of promoting an already existing intestinal tumour and may support the potential of colon cancer cells to metastasize.
Masur
K
K
Institute of Immunology, Witten/Herdecke University, Stockumer Str. 10, 58448 Witten, Germany. kmasur@uni-wh.de
Schwartz
F
F
Entschladen
F
F
Niggemann
B
B
Zaenker
K S
KS
D058892:Adenosine Deaminase Inhibitors; D002273:Carcinogens / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D053767:Glucagon-Like Peptide 2 / Q000008:administration & dosage / Q000494:pharmacology*; D000067758:Glucagon-Like Peptide-2 Receptor; D006023:Glycoproteins / Q000037:antagonists & inhibitors*; D006801:Humans; D018027:Receptors, Glucagon / Q000378:metabolism
D058892:Adenosine Deaminase Inhibitors; D002273:Carcinogens; D054873:Dipeptidyl-Peptidase IV Inhibitors; D053767:Glucagon-Like Peptide 2; D000067758:Glucagon-Like Peptide-2 Receptor; D006023:Glycoproteins; D018027:Receptors, Glucagon; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4