Five types of cancer have been shown to respond to their appropriate embryonic fields. This proposal focuses on the regulation of murine melanoma by the embryonic skin. The mechanism appears to be operative at the time of arrival of normally migrating melanoblasts into the skin. This pattern is suggested by a clear cut difference in tumor incidence following in utero transplantation into specific sites in embryonic skin. In parallel with these in vivo findings, conditioned media from the specific sites in embryonic skin inhibit the growth of melanoma cells in vitro; this can be measured by inhibition of colony size, decreased uptake of tritiated thymidine or other bioassays. In optimal conditions growth of melanoma cells ceases, and the cells have altered morphology and fail to grow again in fresh growth media. The crude activity is stable to boiling and lyophilization and has been localized to two peaks by gel filtration. Proceeding on the hypothesis that our assays with melanoma have detected a developmentally regulated process (i.e. site specific in the skin) we plan to define the tissue specificities of the peaks from gel filtration, select the appropriate peak, purify it and define its biochemical properties by high pressure liquid chromatography, and prepare monoclonal antibodies to it. Virally transformed embryonic cells are a potentially rich source of the activity, and when sufficient amounts are available it will be tested in tumor bearing mice. Antibodies would be used to localize the activity in the embryo.
| Pierce, G B; Parchment, R E (1991) Progression in teratocarcinomas. Basic Life Sci 57:71-8;discussion 78-81 |
| Parchment, R E; Gramzinski, R A; Pierce, G B (1990) Embryonic mechanisms for abrogating the malignancy of cancer cells. Prog Clin Biol Res 354A:331-44 |
| Gramzinski, R A; Parchment, R E; Pierce, G B (1990) Evidence linking programmed cell death in the blastocyst to polyamine oxidation. Differentiation 43:59-65 |
| Parchment, R E; Gramzinski, R A; Pierce, G B (1990) Neoplastic embryoid bodies of embryonal carcinoma C44 as a source of blastocele-like fluid. Differentiation 43:51-8 |
| Pierce, G B; Gramzinski, R A; Parchment, R E (1990) Amine oxidases, programmed cell death, and tissue renewal. Philos Trans R Soc Lond B Biol Sci 327:67-74 |
| Pierce, G B; Lewellyn, A L; Parchment, R E (1989) Mechanism of programmed cell death in the blastocyst. Proc Natl Acad Sci U S A 86:3654-8 |
| Parchment, R E; Pierce, G B (1989) Polyamine oxidation, programmed cell death, and regulation of melanoma in the murine embryonic limb. Cancer Res 49:6680-6 |
| Pierce, G B; Gramzinski, R A; Parchment, R E (1989) Programmed cell death in the blastocyst. Ann N Y Acad Sci 567:182-6 |
| Pierce, G B; Arechaga, J; Muro, C et al. (1988) Differentiation of ICM cells into trophectoderm. Am J Pathol 132:356-64 |
| Pierce, G B; Speers, W C (1988) Tumors as caricatures of the process of tissue renewal: prospects for therapy by directing differentiation. Cancer Res 48:1996-2004 |
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