The relationship between GDNF and integrins in human colorectal cancer cell activity.
OBJECTIVE
This study was performed to determine whether GDNF influences the expression of integrins in colorectal cancer cell lines and to elucidate the mechanisms of adhesion to and invasion of extracellular matrix (ECM) proteins.


METHODS
The expression of integrin subunits and alteration of this expression by GDNF were examined by flow-cytometric analysis and cellular enzyme-linked immunosorbent assay in four human colorectal cancer cell lines. Assays to evaluate adhesion and invasion of cancer cells toward ECM proteins were conducted to investigate whether increased integrin expression affects the interaction between cancer cells and putative integrin ECM ligands.


RESULTS
The RET/GFRalpha-1 receptor complex for GDNF was expressed in all four colorectal cancer cell lines. The expression of the Beta1 integrin subunit in these cells was significantly enhanced by GDNF. The enhancement and associated increase in adhesion and invasion abilities in response to by GDNF were inhibited by blocking the GDNF receptor or the integrin P1 subunit.


CONCLUSIONS
In colorectal cancer, the enhancement of integrin expression by signaling through the GDNF receptor strongly influences adhesion to and invasion of ECM proteins.
Furuta
Akiyoshi
A
First Department of Surgery, Nagoya City University Medical School, Nagoya-city, Japan. akiyoshi11no1@yahoo.co.jp
Funahashi
Hitoshi
H
Sawai
Hirozumi
H
Sato
Mikinori
M
Okada
Yuji
Y
Takeyama
Hiromitsu
H
Manabe
Tadao
T
D002448:Cell Adhesion; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000096:biosynthesis / Q000502:physiology*; D009361:Neoplasm Invasiveness; D014407:Tumor Cells, Cultured
D051100:Glial Cell Line-Derived Neurotrophic Factor; D016023:Integrins