Alterations in integrin expression modulates invasion of pancreatic cancer cells.
BACKGROUND
Factors mediating the invasion of pancreatic cancer cells through the extracellular matrix (ECM) are not fully understood.


METHODS
In this study, sub-populations of the human pancreatic cancer cell line, MiaPaCa-2 were established which displayed differences in invasion, adhesion, anoikis, anchorage-independent growth and integrin expression.


RESULTS
Clone #3 displayed higher invasion with less adhesion, while Clone #8 was less invasive with increased adhesion to ECM proteins compared to MiaPaCa-2. Clone #8 was more sensitive to anoikis than Clone #3 and MiaPaCa-2, and displayed low colony-forming efficiency in an anchorage-independent growth assay. Integrins beta 1, alpha 5 and alpha 6 were over-expressed in Clone #8. Using small interfering RNA (siRNA), integrin beta1 knockdown in Clone #8 cells increased invasion through matrigel and fibronectin, increased motility, decreased adhesion and anoikis. Integrin alpha 5 and alpha 6 knockdown also resulted in increased motility, invasion through matrigel and decreased adhesion.


CONCLUSIONS
Our results suggest that altered expression of integrins interacting with different extracellular matrixes may play a significant role in suppressing the aggressive invasive phenotype. Analysis of these clonal populations of MiaPaCa-2 provides a model for investigations into the invasive properties of pancreatic carcinoma.
Walsh
Naomi
N
National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland. naomi.walsh@dcu.ie
Clynes
Martin
M
Crown
John
J
O'Donovan
Norma
N
D023102:Anoikis / Q000235:genetics; D015153:Blotting, Western; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D016023:Integrins / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering; D014162:Transfection
D016023:Integrins; D034741:RNA, Small Interfering