Interleukin 6 acts as a paracrine growth factor in human mammary carcinoma cell lines.
The effect of interleukin 6 (IL-6) on normal and human mammary carcinoma epithelial cells was studied. IL-6 inhibited the growth of estrogen receptor-positive [ER(+)] breast cancer cell lines, which underwent apoptosis with prolonged treatment. In contrast, ER(-) breast cancer cell lines were resistant to IL-6-mediated growth inhibition. By examining the components of the IL-6 receptor (IL-6R) system, we found that ER(+) breast cancer cells expressed predominantly soluble IL-6Ralpha, whereas the ER(-) breast cancer cells expressed primarily the transmembrane form of the IL-6R, gp130. In addition, detectable levels of IL-6 were secreted into the medium by ER(-) but not ER(+) breast cancer cells. Furthermore, the supernatant obtained from IL-6-secreting, ER(-) cells suppressed the growth of IL-6-sensitive, ER(+) breast cancer cells in a paracrine fashion. Although IL-6 is secreted by ER(-) breast cancer cells, this cytokine does not seem to stimulate the proliferation of these cells in an autocrine fashion. These studies indicate that IL-6 can regulate the growth of normal and transformed human mammary epithelial cells differentially, and that IL-6 secretion by some ER(-) breast cancer cells can function as a paracrine growth factor, suppressing the growth of ER(+) breast cancer cells in vitro.
Chiu
J J
JJ
Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.
Sgagias
M K
MK
Cowan
K H
KH
D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology*; D005260:Female; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D011960:Receptors, Estrogen / Q000032:analysis; D019947:Receptors, Interleukin-6 / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D015850:Interleukin-6; D011960:Receptors, Estrogen; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D013936:Thymidine