alpha-Chemokine growth factors for adenocarcinomas; a synthetic peptide inhibitor for alpha-chemokines inhibits the growth of adenocarcinoma cell lines.
OBJECTIVE
The experiments aimed to determine if alpha-chemokine inhibitors are effective suppressors of the growth of adenocarcinomas, a neoplasm with a high mortality rate.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Fujisawa
N
N
The University of Texas Health Center at Tyler, 75708-3154, USA.
Sakao
Y
Y
Hayashi
S
S
Hadden
W A
WA
Harmon
C L
CL
Miller
E J
EJ
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002630:Chemotactic Factors / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006131:Growth Inhibitors / Q000494:pharmacology*; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D011519:Proto-Oncogenes / Q000187:drug effects*; D014407:Tumor Cells, Cultured
C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; D006131:Growth Inhibitors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D009363:Neoplasm Proteins; D009842:Oligopeptides; C118980:antileukinate