alpha-Chemokine growth factors for adenocarcinomas; a synthetic peptide inhibitor for alpha-chemokines inhibits the growth of adenocarcinoma cell lines
N. Fujisawa et al., alpha-Chemokine growth factors for adenocarcinomas; a synthetic peptide inhibitor for alpha-chemokines inhibits the growth of adenocarcinoma cell lines, J CANC RES, 126(1), 2000, pp. 19-26
Purpose: The experiments aimed to determine if alpha-chemokine inhibitors a
re effective suppressors of the growth of adenocarcinomas, a neoplasm with
a high mortality rats, Methods: Expression of growth-related oncogene (GRO
alpha) and interleukin-8 (IL-8) was determined by enzyme-linked immunosorbe
nt assay. Inhibition alpha-chemokine binding to tumor cells was assessed in
the presence and absence of the hexapeptide, antileukinate, 3-(4,5-Dimethy
lthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were performed to det
ermine the effect of alpha-chemokines, monoclonal antibodies (mAb), and ant
ileukinate on cell proliferation. Finally, antileukinate inhibition of huma
n, lung adenocarcinoma tumor growth, was determined in BALB/c nude mice. Re
sults: All of the adenocarcinomas tested produced either GRO alpha or IL-8
or both. Proliferation of lung, stomach and colon adenocarcinoma cells was
inhibited by anti-GRO alpha mAb and/or anti-IL-8 mAb while recombinant huma
n GRO alpha stimulated the proliferation of lung and stomach adenocarcinoma
s. Antileukinate inhibited GRO alpha binding to specific receptors on adeno
carcinoma cells and inhibited the proliferation of all adenocarcinomas test
ed. Colon-derived adenocarcinomas specifically bound IL-8 and this binding
was also inhibited by antileukinate. Administration of antileukinate in viv
o inhibited the tumor growth of adenocarcinoma A549. Conclusions: GRO alpha
and IL-8 are necessary for the growth of lung, stomach and colon adenocarc
inomas, and can be inhibited by the hexapeptide, antileukinate. The finding
s suggest the possibility of using alpha-chemokine receptor inhibitors in t
he treatment of adenocarcinoma.