Basement membrane proteins play an important role in the invasive processes of human pancreatic cancer cells.
BACKGROUND
The invasive interaction between cells and their matrix has important roles in tumor cell invasion. This study investigated modulation of basement membrane (BM) proteins, especially collagen IV (Coll IV), laminin, and fibronectin (FN), in invasion of human pancreatic cancer cells. Furthermore, we examined the roles of beta(1)-integrins and arginine-glycine-aspartic (RGD)-containing oligopeptide in cell-matrix interactions.


METHODS
Expression of integrins were examined by reverse transcriptase-polymerase chain reaction and flow-cytometric analysis in three human pancreatic cancer cell lines (BxPC-3, PANC-1, and SW1990), respectively. To determine the effect of BM proteins, invasion assays were performed. Western blot analysis for extracellular signal-regulated kinase (ERK) was performed to investigate the involvement of ERK1/2 signaling pathways.


RESULTS
BM proteins significantly enhanced the invasive behavior of pancreatic cancer cells. Pretreatment with anti-beta(1)-integrin antibody suppressed invasion into Matrigel, but RGD-containing peptide inhibited invasion, which was enhanced by Coll IV and FN, not laminin. Treatment with both RGD-containing peptide and beta(1)-integrin antibody inhibited ERK1/2 phosphorylation activated by Coll IV and FN.


CONCLUSIONS
BM proteins have positive actions on the processes of pancreatic cancer cell invasion and cross-talk between BM proteins and beta(1)-integrins widely participates in the multistep processes of pancreatic cancer invasion and metastasis formation.
Sawai
Hirozumi
H
Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. sawai@med.nagoya-cu.ac.jp
Okada
Yuji
Y
Funahashi
Hitoshi
H
Takahashi
Hiroki
H
Matsuo
Yoichi
Y
Yasuda
Akira
A
Ochi
Nobuo
N
Takeyama
Hiromitsu
H
Manabe
Tadao
T
D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000473:pathology* / Q000503:physiopathology*
D024141:Collagen Type IV; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D019012:Integrin beta1; D007797:Laminin; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3