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Inhibition of tumor implantation at sites of trauma by Arg-Gly-Asp containing proteins and peptides

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Abstract

We report on the inhibition of wound implantation by TA3Ha mammary carcinoma cells by Arg-Gly-Asp containing proteins and peptides using a hepatic wedge resection model. Intravenously injected TA3Ha cells rarely form tumor in the liver of syngeneic mice, but after hepatic wedge resection, 45% (107/240) of the mice develop tumors in the hepatic wound. Hepatic wound implantation is significantly (P = 0.01) inhibited by pretreating the cells with whole mouse plasma, but not with fibrinogen-depleted plasma or serum. Tumor inhibition is also achieved by pretreatment of cells with fibrinogen (P = 0.05–0.0004), fibronectin (P = 0.007) and laminin, but not by albumin. The active domain appears to be the RGDS sequence since the deca- and tetrapeptides containing RGDS inhibit wound implantation (P < 0.05). However, the tetrapeptide Arg-Gly-Glu-Ser has no such activity. None of these agents affects ascites tumor formation by the intraperitoneally injected cells, suggesting that anchorage independent growth of cells is not affected. We propose that proteins and peptides containing RGD occupy the binding sites and prevent the cells from interacting with cell adhesion proteins in healing wounds. Proteins and/or peptides containing RGD may be useful for preventing local recurrence in postsurgical cancer patients.

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Authors and Affiliations

  1. Cell Biology Laboratory, Departments of Surgery and Medicine, Evanston Hospital, 2650 Ridge Avenue, 60201, Evanston, IL, USA

    M. Satya Murthy, Brian D. Weiss & Richard J. Miller

  2. Department of Pathology, Cell Biology Laboratory, Evanston Hospital, 2650 Ridge Avenue, 60201, Evanston, IL, USA

    Richard Trueheart

  3. Department of Surgery, Cell Biology Laboratory, Evanston Hospital, 2650 Ridge Avenue, 60201, Evanston, IL, USA

    M. Satya Murthy & Edward F. Scanlon

  4. Department of Surgery, Northwestern University School of Medicine, Chicago, Illinois, USA

    Brian D. Weiss, Richard J. Miller, Richard Trueheart & Edward F. Scanlon

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Murthy, M.S., Weiss, B.D., Miller, R.J. et al. Inhibition of tumor implantation at sites of trauma by Arg-Gly-Asp containing proteins and peptides. Clin Exp Metast 10, 39–47 (1992). https://doi.org/10.1007/BF00163575

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