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Inhibition of tumor metastasis by Arg-Gly-Asp-Ser (RGDS) peptide conjugated with sulfated chitin derivative, SCM-chitin-RGDS

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We have synthesized a new compound in which Arg-Gly-Asp-Ser (RGDS) was conjugated with 6-0-sulfated and 6-O-carboxymethyl-chitin (SCM-chitin), i.e. SCM-chitin-RGDS, and tested the inhibitory effect on lung and liver metastases of three different types of tumors in mice. SCM-chitin-RGDS was more effective for the inhibition of liver metastasis of L5178Y-ML25 lymphoma and lung metastases of colon 26 M3.1 cells than SCM-chitin, RGDS or their mixture. GRGDS peptide, however, required a higher dose (3000 µg) to obtain a sufficiently antimetastatic effect. Intermittent i.v. administration of SCM-chitin-RGDS before or after the i.v. inoculation of L5178Y-ML25 cells caused significant inhibition of liver metastasis as compared with the multiple administration of RGDS, SCM-chitin or untreated control. Co-injection of lymphoma cells with SCM-chitin-RGDS or multiple treatment of SCM-chitin-RGDS after tumor inoculation showed significantly enhanced survival rate. SCM-chitin-RGDS also showed the spontaneous lung metastasis produced by intrafootpad injection of B16-BL6 melanoma cells by the multiple i.v. administrations. These results demonstrate that the conjugation of RGDS peptide with SCM-chitin led to augmentation of therapeutic potential to cancer metastasis, thus implying an importance of the conjugation of cell-adhesive RGDS peptide with structurally heparin-like SCM-chitin, which possesses binding ability to the heparin-binding domain of fibronectin or laminin and extremely low anticoagulant properties.

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Authors and Affiliations

  1. Institute of Immunological Science, Hokkaido University, Kita-ku, Sapporo, Japan

    Hiroyuki Komazawa, Ikuo Saiki, Junya Yoneda, Yung Choon Yoo, Seiichi Tokurat & Ichiro Azuma

  2. Deparmment of Polymer Science, Hokkaido University, Kita-ku, Sapporo, Japan

    Norio Nishi

  3. Fuji Photo Film Company Ltd, Nakanuma, Minamiashigara, Japan

    Naoyuki Nishikawa, Masayoshi Kojima, Mitsunori Ono & Isamu Itoh

Authors
  1. Hiroyuki Komazawa
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  2. Ikuo Saiki
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Komazawa, H., Saiki, I., Nishikawa, N. et al. Inhibition of tumor metastasis by Arg-Gly-Asp-Ser (RGDS) peptide conjugated with sulfated chitin derivative, SCM-chitin-RGDS. Clin Exp Metast 11, 482–491 (1993). https://doi.org/10.1007/BF00054939

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  • DOI: https://doi.org/10.1007/BF00054939

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