Polyethylenimine-coated SPION exhibits potential intrinsic anti-metastatic properties inhibiting migration and invasion of pancreatic tumor cells.
Due to its aggressive behavior, pancreatic cancer is one of the principal causes of cancer-related deaths. The highly metastatic potential of pancreatic tumor cells demands the development of more effective anti-metastatic approaches for this disease. Although polyethylenimine-coated superparamagnetic iron oxide nanoparticles (PEI-coated SPIONs) have been studied for their utility as transfection agents, little is known of their effect on tumor cell biology. Here we demonstrated that PEI-coated SPIONs have potent inhibitory effects on pancreatic tumor cell migration/invasion, through inhibition of Src kinase and decreased expression of MT1-MMP and MMP2 metalloproteinases. When treated with PEI-coated SPIONs, the pancreatic tumor cell line Pan02 showed reduced invadosome density and thus, a decrease in their ability to invade through basement membrane. These nanoparticles temporarily downmodulated microRNA-21, thereby upregulating the cell migration inhibitors PTEN, PDCD4 and Sprouty-1. PEI-coated SPIONs thus show intrinsic, possibly anti-metastatic properties for modulating pancreatic tumor cell migration machinery, which indicates their potential as anti-metastatic agents for treatment of pancreatic cancer.
Department of Immunology and Oncology and NanoBiomedicine Initiative, Centro Nacional de Biotecnología (CNB)/CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
Vladimir
V
Mulens-Arias
Department of Immunology and Oncology and NanoBiomedicine Initiative, Centro Nacional de Biotecnología (CNB)/CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
José Manuel
JM
Rojas
Department of Immunology and Oncology and NanoBiomedicine Initiative, Centro Nacional de Biotecnología (CNB)/CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
Sonia
S
Pérez-Yagüe
Department of Biomaterials and Bioinspired Materials, Instituto de Ciencia de Materiales de Madrid (ICMM)/CSIC, Sor Juana Inés de la Cruz 3, Cantoblanco, 28049 Madrid, Spain.
María del Puerto
Mdel P
Morales
Department of Immunology and Oncology and NanoBiomedicine Initiative, Centro Nacional de Biotecnología (CNB)/CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain. Electronic address: dfbarber@cnb.csic.es.
Domingo F
DF
Barber
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D005290:Ferric Compounds / Q000737:chemistry* / Q000627:therapeutic use*; D018014:Gene Transfer Techniques; D057809:HEK293 Cells; D006801:Humans; D008280:Magnetics; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D035683:MicroRNAs; D053758:Nanoparticles; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000628:therapy*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D011094:Polyethyleneimine / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
D005290:Ferric Compounds; C524940:MIRN21 microRNA, human; D061965:Matrix Metalloproteinase Inhibitors; D035683:MicroRNAs; C000499:ferric oxide; D011094:Polyethyleneimine
Matrix degradation; Nanoparticle; Proliferation; Tumor cell invasion; Tumor cell migration