Human neuroblastoma is a cancer of childhood with a higher incidence of spontaneous regression and differentiation than is found in other cancers. Nevertheless, many patients die of metastatic disease. Amplification of the N-myc oncogene in the tumor cells is highly correlated with metastasis and fatal outcome. In order to understand the above phenomena and to have an impact on the treatment of this disease in the future, we will investigate the cellular and molecular biology of human neuroblastoma growth, differentiation and metastasis in relation to the expression and amplification of the N-myc oncogene. The effects of humoral factors on the survival, growth and differentiation of cultured human neuroblastoma cell lines that do or do not have N-myc oncogene expression or amplification will be examined. Effects of the humoral factors on expression of the N- myc oncogene and expression of neuroblastoma differentiation genes will also be studied. Because cultured cell lines may not reflect all of the biological properties of the tumor cells from which they are derived, the effects of the factors will be examined on growth, differentiation and gene expression of neuroblastoma in primary culture. For these studies, metastatic neuroblastoma will be isolated from bone marrow by two-color immunofluorescence flow cytometry and cell sorting. The roles of N-myc expression and gene amplification in metastasis will be examined in a nude mouse model in which intravenous injection of tumor cells results in lung colonization and intraaortic injection results in bone marrow colonization. Cell lines with and without N-myc expression, N-myc gene amplification, and amplification of drug-resistance genes will be compared. Because ability of a cell to metastasize may result from a process of unstable genetic change, spontaneous and induced mutation rates will be measured in the cell lines. The proposed investigations will define the role of the N-myc oncogene in the growth, differentiation and metastasis of neuroblastoma.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS022039-09
Application #
3403929
Study Section
Pathology A Study Section (PTHA)
Project Start
1985-04-01
Project End
1994-08-31
Budget Start
1992-09-01
Budget End
1994-08-31
Support Year
9
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Arguello, F; Baggs, R B; Graves, B T et al. (1992) Effect of IL-1 on experimental bone/bone-marrow metastases. Int J Cancer 52:802-7
Arguello, F; Furlanetto, R W; Baggs, R B et al. (1992) Incidence and distribution of experimental metastases in mutant mice with defective organ microenvironments (genotypes Sl/Sld and W/Wv). Cancer Res 52:2304-9
Duerst, R E; Rose, D; Frantz, C N (1991) Complement depletion in vitro limits monoclonal antibody 6-19-dependent complement-mediated killing of tumor cells in bone marrow. Exp Hematol 19:863-7
Arguello, F; Baggs, R B; Eskenazi, A E et al. (1991) Vascular anatomy and organ-specific tumor growth as critical factors in the development of metastases and their distribution among organs. Int J Cancer 48:583-90
Arguello, F; Baggs, R B; Duerst, R E et al. (1990) Pathogenesis of vertebral metastasis and epidural spinal cord compression. Cancer 65:98-106
Frantz, C N; Ryan, D H; Cheung, N V et al. (1988) Sensitive detection of rare metastatic human neuroblastoma cells in bone marrow by two-color immunofluorescence and cell sorting. Prog Clin Biol Res 271:249-62
Erickson-Miller, C L; Abboud, C N; Stach, R W et al. (1988) Macrophage colony-stimulating factor in nerve growth factor preparations. J Neurosci Res 19:52-6
Arguello, F; Baggs, R B; Frantz, C N (1988) A murine model of experimental metastasis to bone and bone marrow. Cancer Res 48:6876-81
Ryan, D; Kossover, S; Mitchell, S et al. (1986) Subpopulations of common acute lymphoblastic leukemia antigen-positive lymphoid cells in normal bone marrow identified by hematopoietic differentiation antigens. Blood 68:417-25
Duerst, R E; Ryan, D H; Frantz, C N (1986) Variables affecting the killing of cultured human neuroblastoma cells with monoclonal antibody and complement. Cancer Res 46:3420-5

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