Macrophage Colony-stimulating Factor And Its Receptor Incidence Significance Discussed

Macrophage colony stimulating-factor (M-CSF) and its receptor (M-CSF-R), a pair of signal molecules, play important roles in stimulating the survival, proliferation and differentiation of monocytic lineage cells. Encoded by the proto-oncogene c-fms, M-CSF-R contains a cytoplasmic protein tyrosine kinase domain. M-CSF confers its biological activities by binding with M-CSF-R, through which the signal transduction process is completed as a result of auto-phosphorylation of the receptor tyrosine kinase and activation of a serial of kinases. Previously, the knowledge of M-CSF and M-CSF-R (M-CSF/M-CSF-R) for their biological actions has been limited to hematopoietic system, i.e. they were involved in growing modulation of monocytic progenitors and associated with certain kind of blood diseases. Further studies have demonstrated that, beyond the field of hematopoiesis, this pair of molecules also displayed their biological functions or pathological roles in process of placental development and bone reformation, as well as in development of atherosclerosis, gynecologic malignancy, chronic renal failure (CRF), hepatocellular carcinoma (HCC), and some inflammatory diseases. However, further studies focused on relationship between M-CSF/M-CSF-R and the pathogenic aspects of CRF and HCC were rarely seen, therefor, little is known about the mechanism through which M-CSF/M-CSF-R influence the development or progression of these diseases. This study was proposed to characterize the expression properties and its pathological significance of M-CSF/M-CSF-R in HCC and CRF patients, and to explore the mechanism through which M-CSF/M-CSF-R may display their effects on these diseases. In addition, the possible mechanism for over-expression of M-CSF/M-CSF-R in bone marrow mononuclear cells (BMMC) from leukemic patients was investigated.Autocrine and paracrine are considered as the dominant forms of secretion system, by which the tumor cells enable to escape the immune attack from the host and grow in an autonomy way. An increased expression level of M-CSF-R in human hepatoma tissues as well as an inhibitory effect of both monoclonal antibodies (McAb) against M-CSF and M-CSF-R on growth of hepatoma cells have been reported by others, but the mechanism is unclear. The results of this paper showed that most of the HCC tissues expressed M-CSF/M-CSF-R; the expression levels of M-CSF and M-CSF-R in HCC tissues were significantly higher than that of human fetal tissue (P<0.05, P<0.05) and normal liver tissue (P＜0.01, P＜0.01). Co-expression ratio of M-CSF/M-CSF-R mRNA in HCC tissues reached 60%, while co-expression ratio of M-CSF/M-CSF-R mRNA for 3 hepatoma cell lines reached 100%. Furthermore, a dose dependent inhibitory effect of both McAbs against M-CSF and M-CSF-R on proliferation of hepatoma cells in vitro was observed. The...