Polymeric Delivery of siRNA against Integrin-β1 (CD29) to Reduce Attachment and Migration of Breast Cancer Cells.
Cell surface integrins, which play important roles in the survival, proliferation, migration, and invasion of cancer cells, are a viable target for treatment of metastatic breast cancer. This line of therapy still remains challenging due to the lack of proper identification and validation of effective targets as well as the lack of suitable therapeutic agents for treatment. The focus is on one such molecular target for this purpose, namely integrin-β1, and effective lowering of integrin-β1 levels on a breast cancer model (MDA-MB-231 cells) is achieved by delivering a dicer-substrate short interfering RNA (siRNA) targeting integrin-β1 with lipid-modified low molecular weight polyethylenimine polymers. Reduction of integrin-β1 levels leads to reduced adhesion of MDA-MB-231 cells to extracellular matrix component fibronectin as well as to human bone marrow cells. A reduced migration of the breast cancer cells is also observed after integrin-β1 silencing in "scratch" and "transwell" migration assays. These results highlight the importance of integrin-β1 for the migration of metastatic breast cancer cells by effectively silencing this target with a practical dose of siRNA.
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, T6G 2H1, Canada.
Daniel Nisakar
DN
Meenakshi Sundaram
Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB, T6G 2V2, Canada.
Cezary
C
Kucharski
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, T6G 2H1, Canada.
Manoj B
MB
Parmar
Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB, T6G 2V2, Canada.
Remant Bahadur
RB
Kc
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, T6G 2H1, Canada.|Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB, T6G 2V2, Canada.|Department of Biomedical Engineering, University of Alberta, Edmonton, AB, 2V2, Canada.
Hasan
H
Uludağ
D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D005260:Female; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics*; D009362:Neoplasm Metastasis; D011094:Polyethyleneimine / Q000737:chemistry / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000235:genetics* / Q000627:therapeutic use
D019012:Integrin beta1; D034741:RNA, Small Interfering; D011094:Polyethyleneimine
breast cancer therapy; dicer-substrate siRNA; integrin-β1; lipid-substituted polyethylenimine; migration; siRNA therapy