The laminin alpha-1 chain derived peptide, AG73, increases fibronectin levels in breast and melanoma cancer cells.
Laminin-111 promotes the malignant phenotype, and a 12-mer synthetic peptide (AG73, RKRLQVQLSIRT) from the carboxyl terminus of the alpha1 chain increases B16F10 melanoma metastasis to the lung and liver. Using an antibody array, fibronectin was identified as an up-regulated protein in B16F10 cells after incubation with this peptide. The increased fibronectin is cell-associated with no increase in soluble fibronectin. The AG73 peptide increased the number and size of bone metastases with both B16F10 melanoma and MDA-231 breast carcinoma cells in an intracardiac injection model. Using siRNA transfection, we found that a reduction in fibronectin expression did not reduce bone metastasis in the presence of the metastasis-promoting peptide AG73. We conclude that the laminin peptide AG73 increases metastasis independently of fibronectin expression.
Engbring
Jean A
JA
Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
Hossain
Rydhwana
R
VanOsdol
Sherilyn J
SJ
Kaplan-Singer
Benjamin
B
Wu
Michael
M
Hibino
Suguru
S
Koblinski
Jennifer E
JE
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D005260:Female; D005353:Fibronectins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D015151:Immunoblotting; D007797:Laminin / Q000494:pharmacology*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010446:Peptide Fragments / Q000494:pharmacology*; D040081:Protein Array Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C105786:AG 73; D005353:Fibronectins; D007797:Laminin; D010446:Peptide Fragments; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C084098:laminin A