Inhibition of metastasis of lewis lung carcinoma by urinary trypsin inhibitor in experimental and spontaneous metastasis models

✍ Scribed by Hiroshi Kobayashi; Hiromitsu Shinohara; Michio Fujie; Junko Gotoh; Mariko Itoh; Kinya Takeuchi; Toshihiko Terao

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: French
• Weight: 818 KB
• Volume: 63
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910630326

✦ Synopsis

A purified human urinary trypsin inhibitor (UTI) and its related synthetic peptides were examined to determine whether they could inhibit production of experimental and spontaneous lung metastases by murine Lewis lung carcinoma (3LL) cells. Three peptides, peptide I, peptide 2 and peptide 3, representing the amino acid sequences within the UTI molecule, were synthesized. UTI and peptide 2 inhibited human leukocyte elastase (HLE). UTI and peptide 3 specifically inhibited human and murine plasmin activity. Peptide I had essentially no inhibitory activity. In an in vivo spontaneous metastasis model, multiple S.C. injections of UTI or peptide 3 for 7 days immediately after S. C. tumor cell inoculation significantly inhibited the formation of lung metastasis in C57BL/6 mice in a dosedependent manner. UTI reduced lung tumor colonization more effectively than peptide 3. Peptides I and 2, however, did not affect the formation of lung metastasis. Inhibition of lung metastasis was not due to direct anti-tumor effects of UTI and peptide 3. In an in vivo experimental metastasis assay, multiple S.C. injections of UTI for 7 days after i.v. tumor cell inoculation inhibited metastatic lung tumor colonization, while peptide 3 did not affect metastasis. Peptides I and 2 did not affect the formation of lung metastasis. When examined with an in vitro assay system using a modified Boyden chamber, UTI and peptide 3 suppressed the invasion of tumor cells through Matrigel. UTI and peptide 3 inhibited neither cell proliferation