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Leukemia inhibitory factor binds to human breast cancer cells and stimulates their proliferation. J Interferon Cytokine Res 1995 Oct;15(10):905-13

Date

10/01/1995

Pubmed ID

8564713

DOI

10.1089/jir.1995.15.905

Scopus ID

2-s2.0-0028841064 (requires institutional sign-in at Scopus site)   46 Citations

Abstract

Leukemia inhibitory factor (LIF) is a cytokine that was originally described as a differentiation factor of a murine myeloid leukemia cell line and subsequently found to be an important mediator of embryonic development. Although extensively studied in the hematopoietic system, its effects on solid tumors are generally unknown. In the present study we investigated the role of LIF in human breast cancer cells. Using the 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 radiolabeled LIF demonstrated that MCF-7 cells interacted with this cytokine, and the ligand binding was specific and time, dose, and temperature dependent. In addition, a Scatchard analysis of the data revealed a single class of high-affinity (Kd 0.27 nM) receptors with a density of approximately 430 sites per cell. MCF-7 cells exposed to LIF internalized and degraded the ligand. LIF stimulated the growth of MCF-7 as well as other estrogen-dependent and independent breast cancer cell lines, but the effect on normal breast epithelial lines was less significant. Likewise, it stimulated colony formation by breast cancer cells obtained from five different breast cancer patients in a dose-dependent fashion. These results overall suggest that human breast tumor cells express functional LIF receptors that play a role in breast cancer cell proliferation.

Author List

Estrov Z, Samal B, Lapushin R, Kellokumpu-Lehtinen P, Sahin AA, Kurzrock R, Talpaz M, Aggarwal BB

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Base Sequence
Breast Neoplasms
Cell Division
Growth Inhibitors
Humans
Interleukin-6
Leukemia Inhibitory Factor
Leukemia Inhibitory Factor Receptor alpha Subunit
Lymphokines
Membrane Glycoproteins
Molecular Sequence Data
Neoplasm Proteins
Receptors, Cytokine
Receptors, OSM-LIF
Stimulation, Chemical
Tumor Cells, Cultured
Tumor Stem Cell Assay