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Beschreibung

Macrophage colony-stimulating factor 1 (UniProt: P09603, also known as CSF-1, M-CSF, MCSF, Lanimostim) is encoded by the CSF1 gene (Gene ID: 1435) in human. M-CSF is a single-pass type I membrane glycoprotein that is synthesized with a signal peptide (aa 1-32), which is subsequently cleaved off to generate the mature form that contains a lumenal domain (aa 33-496), a transmembrane domain (aa 497-517), and a cytoplasmic domain (aa 518-554). It can be present as a disulfide-linked homodimer or heterodimer. Two distinct biologically active forms of M-CSF have been described: a membrane-bound and a secreted form that result from alternative splicing of the CSF1 gene. It plays an essential role in the regulation of survival, proliferation, and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. It promotes the release of proinflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. M-CSF is also involved in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and for normal bone development. Its biological effects are mediated via binding to CSF-1R/c-Fms receptor that is expressed by multipotent hematopoietic cells, mononuclear phagocyte progenitor cells, monocytes, tissue macrophages, and osteoclasts. Aberrant expression of M-CSF or CSF-1R is reported to promote cancer cell proliferation, invasion and formation of metastases. Overexpression of M-CSF or CSF-1R is observed in a significant percentage of breast, ovarian, prostate, and endometrial cancers.