A potent anti-metastatic activity of tumor invasion-inhibiting factor-2 and albumin conjugate.
Tumor invasion-inhibiting factor-2 (IIF-2) peptide was chemically conjugated to albumin with 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide hydrochloride. The molar ratio of the covalently linked IIF-2 peptide and albumin in the purified conjugate was 1.4 +/- 0.4, as determined with a radioactive peptide. The conjugate inhibited the invasion of HT1080 and B16FE7 cells in vitro at 40- to 60-fold lower concentrations than IIF-2 peptide. Scatchard analysis of binding data demonstrated that the IIF-2-albumin conjugate bound to HT1080 and B16FE7 cells with Kd values of 240 and 340 nM, respectively. The conjugate suppressed the lung colonization of B16FE7 cells more effectively than the IIF-2 peptide in an experimental metastasis. These results indicate that the covalent linkage of the IIF-2 peptide to a carrier macromolecule provides a structure that enables this peptide to exhibit increased inhibitory action in cancer cell invasion and metastasis, and that IIF-2 exerts its inhibitory action on invasion by binding to a specific binding site on the tumor cell surface.
Isoai
A
A
Research Center, Asahi Glass Co. Ltd., Yokohama, Japan.
Goto-Tsukamoto
H
H
Murakami
K
K
Akedo
H
H
Kumagai
H
H
D000418:Albumins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors; D000818:Animals; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D011506:Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000418:Albumins; D020533:Angiogenesis Inhibitors; D004338:Drug Combinations; D011506:Proteins