The laminin alpha-1 chain derived peptide, AG73, increases fibronectin levels in breast and melanoma cancer cells.

Clin Exp Metastasis

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.

Published: July 2008

AI Article Synopsis

  • Laminin-111 and a synthetic peptide called AG73 enhance the aggressive characteristics of melanoma cells, specifically increasing their ability to spread to the lungs and liver.
  • The peptide AG73 triggers the production of fibronectin in B16F10 melanoma cells, but this increase is confined to cell-associated fibronectin rather than soluble fibronectin in the surrounding environment.
  • Reducing fibronectin levels through siRNA doesn't impact the bone metastasis driven by AG73, indicating that its metastasis-promoting effects operate independently of fibronectin expression.

Article Abstract

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.

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http://dx.doi.org/10.1007/s10585-007-9138-yDOI Listing

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