Hematopoietic growth factors (colony-stimulating factors or CSFs) are known to stimulate the proliferation and maturation of blood cells and their precursors. While the clinical applications of CSFs in stimulating proliferation and maturation of blood cells are well described, its role in effecting non-hematopoietic tumor cell growth remains poorly understood. Additionally, CSFs may have functional effects on the development of non-hematopoietic tissues, particularly those of neural cell origin. The goal of this application is to define and characterize the regulatory effects of two specific human CSFs on non- hematopoietic cells (i.e., granulocyte-macrophage colony-stimulating factor [GM-CSF] and granulocyte colony-stimulating factor [G-CSF]). These studies will determine GM-CSF and G-CSF responsiveness and receptor expression on primary human melanoma and neuroblastomas in both in vitro clonogenic assays systems, as well as in vivo transplantation studies using human tumor cells in severe combined immune deficiency (SCID) mice. The second goal of this proposal is to characterize a functional role of GM-CSF, G-CSF, and their respective receptors in the development of the central nervous system and in neurological disorders.
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