Journal of Bioactive and Compatible Polymers

 

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Journal of Bioactive and Compatible Polymers, Vol. 8, No. 3, 258-274 (1993)
DOI: 10.1177/088391159300800305

Inhibition of Tumor Metastasis by a Synthetic Polymer Containing a Cell-Adhesive RGDS Peptide

Hiroyuki Komazawa

Institute of Immunological Science Hokkaido University Kita-15, Nishi-7 Kita-ku, Sapporo 060, Japan

Ikuo Saiki

Institute of Immunological Science Hokkaido University Kita-15, Nishi-7 Kita-ku, Sapporo 060, Japan

YU Igarashi

Institute of Immunological Science Hokkaido University Kita-15, Nishi-7 Kita-ku, Sapporo 060, Japan

Ichiro Azuma

Institute of Immunological Science Hokkaido University Kita-15, Nishi-7 Kita-ku, Sapporo 060, Japan

Masayoshi Kojima

Fuji Photo Film Co., Ltd. Ashigara Research Laboratories 210 Nakanuma, Minamiashigara, 250-01, Japan

Atsushi Orikasa

Fuji Photo Film Co., Ltd. Ashigara Research Laboratories 210 Nakanuma, Minamiashigara, 250-01, Japan

Mitsunori Ono

Fuji Photo Film Co., Ltd. Ashigara Research Laboratories 210 Nakanuma, Minamiashigara, 250-01, Japan

Isamu Itoh

Fuji Photo Film Co., Ltd. Ashigara Research Laboratories 210 Nakanuma, Minamiashigara, 250-01, Japan

A water soluble polymer containing cell adhesive Arg-Gly-Asp- Ser (RGDS) sequence, i.e., poly(carboxyethylmethacrylamide-RGDS) conjugate [poly(CEMA-RGDS)], was synthesized. Poly(CEMA-RGDS) inhibited lung metastasis of B16-BL6 melanoma cells in a dose-dependent manner (20-1000 µg) and liver metastasis of L5178YML25 lymphoma cells. A mixture of poly- (CEMA) and RGDS peptide or poly(CEMA) alone did not show any inhibitory effect on lung metastasis. The Gly-Arg-Gly-Asp-Ser (GRGDS) peptide required high doses (3000 µ g) to obtain a sufficient antimetastatic effect. An in vitro study showed that poly(CEMA-RGDS) as well as RGDS + poly(CEMA) gave similar inhibition of B16-BL6 cell invasion into reconstituted basement mem brane Matrigel. Intermittent i.v. administration of poly(CEMA-RGDS) after in oculation with B16-BL6 cells caused significant inhibition of spontaneous lung metastasis as compared with the multiple administration of RGDS, poly- (CEMA) or untreated control. These results demonstrate that the conjugation


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