The fate of human malignant melanoma cells transplanted into zebrafish embryos: Assessment of migration and cell division in the absence of tumor formation

Lisa M.J. Lee, Elisabeth A. Seftor, Gregory Bonde, Robert A. Cornell, Mary J.C. Hendrix*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

187 Scopus citations

Abstract

Certain aggressive melanoma cell lines exhibit a dedifferentiated phenotype, expressing genes that are characteristic of various cell types including endothelial, neural, and stem cells. Moreover, we have shown that aggressive melanoma cells can participate in neovascularization in vivo and vasculogenic mimicry in vitro, demonstrating that these cells respond to microenvironmental cues and manifest developmental plasticity. To explore this plasticity further, we transplanted human metastatic melanoma cells into zebrafish blastula-stage embryos and monitored their behavior post-transplantation. The data show that human metastatic melanoma cells placed in the zebrafish embryo survive, exhibit motility, and divide. The melanoma cells do not form tumors nor integrate into host organs, but instead become scattered throughout the embryo in interstitial spaces, reflecting the dedifferentiated state of the cancer cells. In contrast to the fate of melanoma cells, human melanocytes transplanted into zebrafish embryos most frequently become distributed to their normal microenvironment of the skin, revealing that the zebrafish embryo contains possible homing cues that can be interpreted by normal human cells. Finally, we show that within the zebrafish embryo, metastatic melanoma cells retain their dedifferentiated phenotype. These results demonstrate the utility of the zebrafish embryonic model for the study of tumor cell plasticity and suggest that this experimental paradigm can be a powerful one in which to investigate tumor-microenvironment interactions.

Original languageEnglish (US)
Pages (from-to)1560-1570
Number of pages11
JournalDevelopmental Dynamics
Volume233
Issue number4
DOIs
StatePublished - Aug 2005

Keywords

  • Human metastatic melanoma
  • Tumor cell plasticity
  • Tumor-microenvironment interactions
  • Zebrafish embryo

ASJC Scopus subject areas

  • Developmental Biology

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