α-Chemokine growth factors for adenocarcinomas; a synthetic peptide inhibitor for α-chemokines inhibits the growth of adenocarcinoma cell lines

• Published in: Journal of cancer research and clinical oncology Vol. 126; no. 1; pp. 19 - 26
• Main Authors: FUJISAWA, N, SAKAO, Y, HAYASHI, S, HADDEN, W. A, HARMON, C. L, MILLER, E. J
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.01.2000
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Animals; Antineoplastic agents; Biological and medical sciences; Chemokine CXCL1; Chemokines, CXC - antagonists & inhibitors; Chemokines, CXC - metabolism; Chemotactic Factors - metabolism; Enzyme-Linked Immunosorbent Assay; General aspects; Growth Inhibitors - pharmacology; Growth Substances - metabolism; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-8 - metabolism; Medical sciences; Mice; Mice, Inbred BALB C; Neoplasm Proteins - pharmacology; Oligopeptides - pharmacology; Pharmacology. Drug treatments; Proto-Oncogenes - drug effects; Tumor Cells, Cultured; Adenocarcinoma; Antineoplastic agent; Human; Cell proliferation; Protein inhibitor; Cytokine; Malignant tumor; Immunity; In vitro; Biological activity; Chemokine; Biological fixation; Established cell line; Recombinant protein; Tumor cell; Interleukin 8; Growth factor; Biological receptor
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/PL00008460

The experiments aimed to determine if alpha-chemokine inhibitors are effective suppressors of the growth of adenocarcinomas, a neoplasm with a high mortality rate. Expression of growth-related oncogene (GROalpha) and interleukin-8 (IL-8) was determined by enzyme-linked immunosorbent assay. Inhibition of alpha-chemokine binding to tumor cells was assessed in the presence and absence of the hexapeptide, antileukinate. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were performed to determine the effect of alpha-chemokines, monoclonal antibodies (mAb), and antileukinate on cell proliferation. Finally, antileukinate inhibition of human, lung adenocarcinoma tumor growth, was determined in BALB/c nude mice. All of the adenocarcinomas tested produced either GROalpha or IL-8 or both. Proliferation of lung, stomach and colon adenocarcinoma cells was inhibited by anti-GROalpha mAb and/or anti-IL-8 mAb while recombinant human GROalpha stimulated the proliferation of lung and stomach adenocarcinomas. Antileukinate inhibited GROalpha binding to specific receptors on adenocarcinoma cells and inhibited the proliferation of all adenocarcinomas tested. Colon-derived adenocarcinomas specifically bound IL-8 and this binding was also inhibited by antileukinate. Administration of antileukinate in vivo inhibited the tumor growth of adenocarcinoma A549. GROalpha and IL-8 are necessary for the growth of lung, stomach and colon adenocarcinomas, and can be inhibited by the hexapeptide, antileukinate. The findings suggest the possibility of using alpha-chemokine receptor inhibitors in the treatment of adenocarcinoma.