Synthetic peptides inhibit adhesion of human tumor cells to extracellular matrix proteins

I. B. DeRoock, M. E. Pennington, T. C. Sroka, K. S. Lam, G. T. Bowden, E. L. Bair, A. E. Cress

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Human tumor cell progression and metastasis are partially dependent on the ability of a tumor cell to adhere to the proteins of the extracellular matrix (ECM) and survive at the distant location. Six novel D-amino acid-containing peptides were analyzed for their ability to adhere to human prostate tumor cells, support tumor cell adhesion, and inhibit tumor cell adhesion to ECM proteins or human dermal fibroblasts. Of these, two peptides called RZ-3 (kmviywkag) and HYD-1 (kikmviswkg) bound to tumor cell surfaces and compared favorably with the previously reported AG-73 (RKRLQVQLSIRT) L-amino acid peptide, as determined by fluorescence-activated cell sorting analysis. A scrambled peptide derivative of HYD-1, called HYDS-1 (wiksmkivkg), was not active. The RZ-3, HYD-1, and AG-73 peptides supported maximal cancer cell adhesion at 5 μg, 10 μg, and 50 μg/well, respectively. The ECM proteins fibronectin, laminin 1, and collagen IV supported maximal cell adhesion at 1 μg, >10 μg, and 50 μg/well, respectively. Prostate tumor cell adhesion to immobilized RZ-3 and HYD-1 peptides was inhibited by α2-6- and β1-integrin-blocking antibodies. Conversely, tumor cell adhesion to a β1-integrin-specific antibody was blocked by both RZ-3 and HYD-1. Epithelial cell adhesion to dermal fibroblasts was inhibited by HYD-1 and unaffected by the scrambled peptide, HYDS-1. Cell adhesion to immobilized peptides was unaffected by EDTA. The soluble RZ-3 and HYD-1 peptides inhibited tumor cell adhesion to each of the immobilized four ECM proteins (1.0 μg/well) in a time- and concentration-dependent manner. The IC50 of the RZ-3 peptide for blocking adhesion to fibronectin, laminin 1, laminin 5, and collagen IV was 2.4 μg, 1.8 μg, 4.6 μg, and 2.8 μg/well, respectively. The IC50 of the HYD-1 peptide for blocking adhesion to fibronectin, laminin 1, laminin 5, and collagen IV was 6.9 μg, 5.7 μg, >10 μg, and 6.2 μ/well, respectively. Taken together, these results indicate that RZ-3 and HYD-1 are biologically active D-amino acid-containing peptides that can themselves support tumor cell adhesion and can inhibit tumor cell adhesion to immobilized ECM proteins or dermal fibroblasts.

Original languageEnglish (US)
Pages (from-to)3308-3313
Number of pages6
JournalCancer Research
Volume61
Issue number8
StatePublished - Apr 15 2001

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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