Reprogramming of melanoma cells by embryonic microenvironments.
In recent years, the reversion of the cancer phenotype of human melanoma cells in developing zebrafish and chick embryos has been reported. The aim of this review is to revise these and other related contributions regarding the regulation of embryonic cancer and to provide a framework with which to understand results from our laboratory on the interactions of human melanoma cells with post-implanted mouse embryos cultured in vitro. To this end, we used the A375 human melanoma cell line transfected with the green fluorescent protein (GFP) gene. Labeled cells were transplanted onto the surface of the developing visceral endoderm of 7.5 dpc mouse embryos. Subsequently, we cultured the transplanted embryos for three days and monitored the movements of GFP labeled human melanoma cells by confocal microscopy. Our results show that ectopic melanoma cells internalize and migrate inside the embryo body in a way reminiscent of neural crest cells. The absence of localized tumor growth after 72 hours of in vitro embryo co-culture suggests that malignant phenotype inhibiting factors are active at the gastrulating stage and during early organogenesis. These results complement previous reports of growth regulation of B16 mouse melanoma cells by 10 dpc mouse embryonic skin (Gerschenson et al., 1986). Further research is required to elucidate the final fate of melanoma cells in mammalian embryos and the details of the signaling pathways underlying tumor growth regulation. Understanding regulation of melanoma cells by young embryos could represent a starting point for a developmental theory of the pathogenesis of melanoma, and for future developments of more physiologically-based anticancer therapies for this and indeed, other types of aggressive tumor.
Díez-Torre
Alejandro
A
Laboratory of Stem Cells, Development and Cancer, Department of Cell Biology and Histology and Analytical and High Resolution Biomedical Microscopy Core Facility, University of the Basque Country, Leioa, Vizcaya, Spain.
Andrade
Ricardo
R
Eguizábal
Cristina
C
López
Elixabete
E
Arluzea
Jon
J
Silió
Margarita
M
Aréchaga
Juan
J
D000818:Animals; D045744:Cell Line, Tumor; D046149:Embryo Culture Techniques; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism / Q000473:pathology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008546:Melanoma, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018613:Microscopy, Confocal; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012196:Review Literature as Topic; D013997:Time Factors; D014183:Transplantation, Heterologous
D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins