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Nonhematopoietic tumor cell lines express stem cell factor and display
c-kit receptors
AM Turner, KM Zsebo, F Martin, FW Jacobsen, LG Bennett and VC Broudy
Department of Medicine, University of Washington, Seattle 98195.
Human stem cell factor (SCF) acts in the presence of other growth factors
to stimulate the growth of primitive hematopoietic progenitor cells. These
effects are performed by activation of the SCF receptor, c- kit. Because of
the potential use of SCF in patients undergoing chemotherapy and bone
marrow transplantation, the effect of SCF on nonhematopoietic tumors
requires investigation. To determine whether human tumor cell lines display
c-kit receptors, we performed binding experiments with 125I-SCF on a breast
carcinoma cell line (Du4475), a gastric carcinoma cell line (KATO III), a
melanoma cell line (HTT144), as well as two small cell lung carcinoma cell
lines (H69 and H128). The biologic effect of SCF on tumor cell lines was
assessed by its ability to stimulate tritiated thymidine uptake and to
enhance colony growth in methylcellulose. The breast carcinoma cell line,
Du4475, as well as two small cell lung carcinoma cell lines, H69 and H128,
exhibit high- affinity c-kit receptors with approximate binding affinities
of 40, 100, and 90 pmol/L, respectively. The number of high-affinity
receptors per cell ranged from 700 to 9,500. The gastric carcinoma cell
line, as well as the melanoma cell line, showed trace binding of 125I-SCF.
In the presence of SCF alone, or in combination with granulocyte-
macrophage colony-stimulating factor or interleukin-3, there was less than
a 17% increase in the colony growth of Du4475, H69, or H128 cell lines.
Postulating that the lack of growth response could be secondary to
endogenous SCF production by the tumor cell lines, we used an RNAse
protection assay to determine whether the tumor cell lines contain SCF
messenger RNA (mRNA). In addition, we tested tumor cell line supernatants
for the presence of secreted SCF protein by enzyme immunoassay, and
analyzed the tumor cell lines for membrane-bound SCF by indirect
immunofluorescence. Our results show that the Du4475, H69, and H128 cell
lines, as well as a melanoma cell line (HTT144), have multiple copies of
SCF mRNA. Soluble SCF protein was detected in the cell supernatants in the
Du4475 and H69 cell lines and SCF was found on the surface of all four cell
lines. These data show that some human solid tumor cell lines display
high-affinity c-kit receptors and produce SCF, which can be detected on the
cell surface. These results suggest the possibility that autocrine
production of SCF by c-kit receptor-bearing tumor cells may enhance cell
growth in tumor cell lines.
Volume 80,
Issue 2,
pp. 374-381,
07/15/1992
Copyright © 1992 by The American Society of Hematology
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