Stimulation of ovarian tumor cell proliferation with monocyte products including interleukin-1, interleukin-6, and tumor necrosis factor-alpha.
OBJECTIVE
We investigated whether monocyte-derived factors could stimulate the growth of ovarian cancer cells.


METHODS
Human peripheral blood monocytes or human monocyte-like cell lines THP-1 and U-937 were cultured with or without macrophage colony-stimulating factor, lipopolysaccharide, or phorbol myristate acetate. Culture supernatants or recombinant cytokines were assayed for growth stimulation of ovarian cancer cell lines by tritium-thymidine incorporation and direct cell counts followed by statistical analysis with Student t test.


RESULTS
Conditioned medium from peripheral blood monocytes or from THP-1 or U-937 cells stimulated ovarian cancer cell growth. Interleukin-1 alpha, tumor necrosis factor-alpha, and interleukin-6 also stimulated ovarian cancer cell growth, whereas macrophage, granulocyte, and granulocyte-macrophage colony-stimulating factor did not. Concentrations of tumor necrosis factor, interleukin-1, and interleukin-6 in conditioned medium could not account for all the growth stimulation, and activity remained after neutralization of tumor necrosis factor, interleukin-1, and interleukin-6 with antibodies.


CONCLUSIONS
Interleukin-1, interleukin-6, tumor necrosis factor, and additional monocyte factor(s) could provide paracrine growth stimulation when monocytes are attracted to ovarian cancers that produce macrophage colony-stimulating factor.
Wu
S
S
Department of Medicine, Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, NC 27710.
Rodabaugh
K
K
Martinez-Maza
O
O
Watson
J M
JM
Silberstein
D S
DS
Boyer
C M
CM
Peters
W P
WP
Weinberg
J B
JB
Berek
J S
JS
Bast
R C
RC
D002455:Cell Division; D003470:Culture Media; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D008070:Lipopolysaccharides; D009000:Monocytes / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D003470:Culture Media; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate