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

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Abstract

Laminin-111 promotes the malignant phenotype, and a 12-mer synthetic peptide (AG73, RKRLQVQLSIRT) from the carboxyl terminus of the α1 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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Abbreviations

GFP:

Green fluorescent protein

FBS:

Fetal bovine serum

PBS:

Phosphate buffered saline

q-PCR:

Quantitative-polymerase chain reaction

H + E:

Hematoxilin and eosin

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Acknowledgments

We thank Drs. Hynda Kleinman for her expert advice and guidance, Takashi Nakamura for his expertise in scanning the antibody microarray, Matthew P. Hoffman and Melinda Larsen for help with siRNA methodology and primer design, Danny Welch for the MDA-231 breast cancer cells expressing GFP, and Kenneth M. Yamada for providing the rabbit anti-human fibronectin antibody.

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Author notes

  1. Jean A. Engbring

    Present address: Bioqual, Inc., Rockville, MD, USA

  2. Suguru Hibino

    Present address: Fourth Department of Internal Medicine, Nippon Medical School, Tokyo, Japan

  3. Jennifer E. Koblinski

    Present address: Breast Cancer Research Program, Department of Pathology, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Institute, Northwestern University, 303 E. Superior St., Lurie 4-105, Chicago, IL, 60611, USA

Authors and Affiliations

  1. 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

    Jean A. Engbring, Rydhwana Hossain, Sherilyn J. VanOsdol, Benjamin Kaplan-Singer, Michael Wu, Suguru Hibino & Jennifer E. Koblinski

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  1. Jean A. Engbring
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  2. Rydhwana Hossain
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  3. Sherilyn J. VanOsdol
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  7. Jennifer E. Koblinski
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Corresponding author

Correspondence to Jennifer E. Koblinski.

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Engbring, J.A., Hossain, R., VanOsdol, S.J. et al. The laminin α-1 chain derived peptide, AG73, increases fibronectin levels in breast and melanoma cancer cells. Clin Exp Metastasis 25, 241–252 (2008). https://doi.org/10.1007/s10585-007-9138-y

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  • DOI: https://doi.org/10.1007/s10585-007-9138-y

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