EXPRESSION OF LEUKEMIA INHIBITORY FACTOR AND ITS RECEPTOR IN BREAST-CANCER - A POTENTIAL AUTOCRINE AND PARACRINE GROWTH-REGULATORY MECHANISM

Leukemia inhibitory factor (LIF) is a pluripotent cytokine which has a diverse array of effects on hematopoietic and epithelial cells. Depen ding on the nature of the target cells, these effects can be growth-st imulatory or growth-inhibitory Receptors for leukemia inhibitory facto r (LIFR) have been identified on a variety of hematopoietic and epithe lial cells. We have recently demonstrated in vitro growth stimulation of human breast cancer cells, both primary tumors and cultured cell li nes, by LIE To begin to understand the in vivo relevance of these obse rvations, we investigated the expression of LIF and LIFR in human brea st cancer specimens. Specimens from 50 cases were immunostained with m ouse monoclonal antibodies D62.3 and M1 (to stain for LIF and LIFR, re spectively), LIF expression was observed in 78% of the specimens and c orrelated with favorable biological features, i.e. low S-phase fractio n (SPF) (P = 0.001) and diploidy (P = 0.08). LIFR expression was obser ved in 80% of the tumors and correlated with the presence of estrogen receptor (ER) (P = 0.04) and diploidy (P = 0.07). Coexpression of LIF and LIFR was associated with diploidy (P = 0.02) and low SPF (P = 0.05 ). LIF staining was primarily cytoplasmic whereas LIFR staining was cy toplasmic in the majority of cases and membranous in a minority of cas es. The presence of LIFR in the primary tumor specimens correlated wit h the growth stimulation of tumor cells (derived from the same specime ns) by exogenous LIF in methylcellulose colony assays. The findings su pport a widespread but probably complex role for LIF and LIFR in breas t tumor growth regulation which should be investigated in greater deta il in larger cohorts of tumors.