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 β1 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. Conclusion 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.
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Dublin City University ->
Subject = Medical Sciences: Cancer
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Dublin City University ->
Publication Type = Article
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Dublin City University ->
Subject = Biological Sciences: Cell biology
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Dublin City University ->
Status = Published
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Dublin City University ->
Subject = Biological Sciences
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Dublin City University ->
Subject = Medical Sciences
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Dublin City University ->
DCU Faculties and Centres = Research Initiatives and Centres: National Institute for Cellular Biotechnology (NICB)
Ireland ->
Dublin City University ->
DCU Faculties and Centres = Research Initiatives and Centres
Norma O'Donovan,
John Crown,
Martin Clynes,
Naomi Walsh