The road less travelled: c-kit and stem cell factor.
Autocrine stimulation of growth factor receptors by autonomously produced ligands regulates different aspects of cellular transformation and progression. In several tumors, including gliomas, multiple autocrine systems are activated and may exert different functions in the malignant transformation process. The c-kit proto-oncogene is widely expressed in human gliomas, and it may be activated by its co-expressed ligand, stem cell factor (SCF). Studies in glioma cell lines as well as different tumor types suggest the possibility of intracellular interactions of c-kit with SCF. Although c-kit and SCF may not play a primary and causal role in the initiation and progression of glial tumors they may still be contributing factors in glioma biology. It can be hypothesized that the parallel activation of several autocrine systems including some of which have found less attention in gliomas, such as c-kit/SCF, could compromise the efficacy of therapies targeting different autocrine loops. A better understanding of the multiplicity and mechanisms of autocrine stimulation has implications for the development of new therapies interfering with autocrine tumor cell growth.
Hamel
W
W
Neurochirurgische Klinik, Universitätskrankenhaus Eppendorf, Hamburg, Germany.
Westphal
M
M
D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D009857:Oncogenes / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000502:physiology*; D019089:Stem Cell Factor / Q000096:biosynthesis / Q000502:physiology*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit