Alteration of integrin expression by glial cell line-derived neurotrophic factor (GDNF) in human pancreatic cancer cells.
BACKGROUND
Pancreatic cancer cells express a number of functionally active integrins that are related to their adhesive and invasive abilities.


OBJECTIVE
To determine whether glial cell line-derived neurotrophic factor (GDNF) influences the expression of integrins in pancreatic cancer cell lines and to elucidate the mechanisms of adhesion and invasion to extracellular matrix (ECM) proteins.


METHODS
The expression of integrin subunits and the alteration of their expression by GDNF were examined by flow-cytometric analysis and cellular enzyme-linked immunosorbent assay in pancreatic cancer cell lines (MIA PaCa-2 and BxPC-3). Assays of adhesion and invasion of cancer cells to ECM proteins were conducted to investigate whether increased integrin expression affects the interaction between cancer cells and putative integrin ECM ligands.


RESULTS
Expression of some of the integrin subunits in pancreatic cancer cells was enhanced by GDNF. The enhancement and associated increase in adhesive and invasive ability by GDNF were inhibited by blocking the GDNF receptor or the integrin beta1 subunit.


CONCLUSIONS
In pancreatic cancer, the enhancement of integrin expression by GDNF signaling through the GDNF receptor strongly influences adhesion and invasion to ECM proteins.
Funahashi
Hitoshi
H
First Department of Surgery, Nagoya City University Medical School, Nagoya, Japan. funa84@med.nagoya-cu.ac.jp
Takeyama
Hiromitsu
H
Sawai
Hirozumi
H
Furuta
Akiyoshi
A
Sato
Mikinori
M
Okada
Yuji
Y
Hayakawa
Tetsushi
T
Tanaka
Moritsugu
M
Manabe
Tadao
T
D000906:Antibodies / Q000494:pharmacology; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D005434:Flow Cytometry; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006801:Humans; D019012:Integrin beta1 / Q000276:immunology; D016023:Integrins / Q000096:biosynthesis*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D021122:Protein Subunits / Q000096:biosynthesis / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000906:Antibodies; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D019012:Integrin beta1; D016023:Integrins; D009414:Nerve Growth Factors; D021122:Protein Subunits; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases