Abstract: The present invention establishes the fact that the degradation of SP to SP(1-4) by endogenous NEP in BM stroma can be a mediator of hematopoietic stimulation by stem cell factor (SCF) and induce the production of TGF-&bgr; and TNF-&agr; in BM stroma. The present invention establishes that compositions containing the SP(1-4) polypeptide, or NEP genetic elements, can be used to slow and or stop the rapid growth of stem and progenitor cells thus protecting them from the deleterious effects of cancer therapy. Hence, the polynucleotides and proteins of the present invention may be used to protect stem cells from the toxic effects of chemo- and radio-therapy, in those undergoing, or about to undergo such cancer related treatments. Also provided are compositions containing NEP antisense sequences and antibodies used for the increased proliferation and differentiation of stem and/or progenitor cells in those whom have already undergone chemo- and/or radio-therapy.

Abstract: The present invention discloses the cloning of a new cDNA, HGFIN, from stimulated BM stromal cells that was retrieved with a probe specific for the neurokinin-1 (NK-1) receptor. The novel gene, HGFIN, encodes a protein receptor that is involved in the regulation of hematopoietic proliferation and differentiation. HGFIN is implicated in the treatment of hyperproliferative disorders, particularly cancer, because it acts to suppress the proliferating cells.

Abstract: Bone marrow (BM) is the major organ where immune cells are derived. Homeostasis in the BM is maintained by inter- and intra-cellular interactions by the various subsets of BM cells. The present invention discloses the cloning of a new cDNA from stimulated BM stromal cells that was retrieved with a probe specific for the neurokinin-1 (NK-1) receptor. The cloned cDNA was designated ‘Hematopoietic Growth Factor Inducible Neurokinin-1 type’ (HGFIN) gene based on its expression in differentiated hematopoietic cells. Hence, the present invention provides a novel gene, HGFIN, which encodes a protein receptor that is involved in the regulation of hematopoietic proliferation and differentiation.

Abstract: Compositions and methods are provided for identifying novel therapeutic agents for the treatment of breast cancer, bone marrow metastasis, pain, arthritis, aggressive behavior, depression, and certain hematopoietic disorders. Disclosed are promoters and 3′ regulatory regions of genes whose expression differs in malignant cells as compared with non-malignant cells. These include PPT-I, NK-2 and SP-R.