LEUKEMIA INHIBITORY FACTOR BINDS TO HUMAN BREAST-CANCER CELLS AND STIMULATES THEIR PROLIFERATION

Leukemia inhibitory factor (LIF) is a cytokine that was originally des cribed as a differentiation factor of a murine myeloid leukemia cell l ine and subsequently found to be an important mediator of embryonic de velopment, Although extensively studied in the hematopoietic system, i ts effects on solid tumors are generally unknown, In the present study we investigated the role of LIF in human breast cancer cells, Using t he reverse transcriptase-polymerase chain reaction, we found that the human breast carcinoma MCF-7 cell line expressed the message for both LIF receptor and its signal-transducing protein gp130, suggesting that these receptors might be biologically active, Binding studies with ra diolabeled LIF demonstrated that MCF-7 cells interacted with this cyto kine, and the ligand binding was specific and time, dose, and temperat ure dependent, In addition, a Scatchard analysis of the data revealed a single class of high-affinity (K-d 0.27 nM) receptors with a density of approximately 430 sites per cell, MCF-7 cells exposed to LIF inter nalized and degraded the ligand, LIF stimulated the growth of MCF-7 as well as other estrogen-dependent and independent breast cancer cell l ines, but the effect on normal breast epithelial lines was less signif icant, Likewise, it stimulated colony formation by breast cancer cells obtained from five different breast cancer patients in a dose-depende nt fashion, These results overall suggest that human breast tumor cell s express functional LIF receptors that play a role in breast cancer c ell proliferation.