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Visualizing Engrafted Human Cancer and Therapy Responses in Immunodeficient Zebrafish.

Publication ,  Journal Article
Yan, C; Brunson, DC; Tang, Q; Do, D; Iftimia, NA; Moore, JC; Hayes, MN; Welker, AM; Garcia, EG; Dubash, TD; Hong, X; Drapkin, BJ; Myers, DT ...
Published in: Cell
June 13, 2019

Xenograft cell transplantation into immunodeficient mice has become the gold standard for assessing pre-clinical efficacy of cancer drugs, yet direct visualization of single-cell phenotypes is difficult. Here, we report an optically-clear prkdc-/-, il2rga-/- zebrafish that lacks adaptive and natural killer immune cells, can engraft a wide array of human cancers at 37°C, and permits the dynamic visualization of single engrafted cells. For example, photoconversion cell-lineage tracing identified migratory and proliferative cell states in human rhabdomyosarcoma, a pediatric cancer of muscle. Additional experiments identified the preclinical efficacy of combination olaparib PARP inhibitor and temozolomide DNA-damaging agent as an effective therapy for rhabdomyosarcoma and visualized therapeutic responses using a four-color FUCCI cell-cycle fluorescent reporter. These experiments identified that combination treatment arrested rhabdomyosarcoma cells in the G2 cell cycle prior to induction of apoptosis. Finally, patient-derived xenografts could be engrafted into our model, opening new avenues for developing personalized therapeutic approaches in the future.

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Published In

Cell

DOI

EISSN

1097-4172

Publication Date

June 13, 2019

Volume

177

Issue

7

Start / End Page

1903 / 1914.e14

Location

United States

Related Subject Headings

  • Zebrafish
  • Xenograft Model Antitumor Assays
  • Temozolomide
  • Rhabdomyosarcoma
  • Piperazines
  • Phthalazines
  • Neoplasm Transplantation
  • Muscle Neoplasms
  • Male
  • K562 Cells
 

Citation

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Yan, C., Brunson, D. C., Tang, Q., Do, D., Iftimia, N. A., Moore, J. C., … Langenau, D. M. (2019). Visualizing Engrafted Human Cancer and Therapy Responses in Immunodeficient Zebrafish. Cell, 177(7), 1903-1914.e14. https://doi.org/10.1016/j.cell.2019.04.004
Yan, Chuan, Dalton C. Brunson, Qin Tang, Daniel Do, Nicolae A. Iftimia, John C. Moore, Madeline N. Hayes, et al. “Visualizing Engrafted Human Cancer and Therapy Responses in Immunodeficient Zebrafish.Cell 177, no. 7 (June 13, 2019): 1903-1914.e14. https://doi.org/10.1016/j.cell.2019.04.004.
Yan C, Brunson DC, Tang Q, Do D, Iftimia NA, Moore JC, et al. Visualizing Engrafted Human Cancer and Therapy Responses in Immunodeficient Zebrafish. Cell. 2019 Jun 13;177(7):1903-1914.e14.
Yan, Chuan, et al. “Visualizing Engrafted Human Cancer and Therapy Responses in Immunodeficient Zebrafish.Cell, vol. 177, no. 7, June 2019, pp. 1903-1914.e14. Pubmed, doi:10.1016/j.cell.2019.04.004.
Yan C, Brunson DC, Tang Q, Do D, Iftimia NA, Moore JC, Hayes MN, Welker AM, Garcia EG, Dubash TD, Hong X, Drapkin BJ, Myers DT, Phat S, Volorio A, Marvin DL, Ligorio M, Dershowitz L, McCarthy KM, Karabacak MN, Fletcher JA, Sgroi DC, Iafrate JA, Maheswaran S, Dyson NJ, Haber DA, Rawls JF, Langenau DM. Visualizing Engrafted Human Cancer and Therapy Responses in Immunodeficient Zebrafish. Cell. 2019 Jun 13;177(7):1903-1914.e14.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

June 13, 2019

Volume

177

Issue

7

Start / End Page

1903 / 1914.e14

Location

United States

Related Subject Headings

  • Zebrafish
  • Xenograft Model Antitumor Assays
  • Temozolomide
  • Rhabdomyosarcoma
  • Piperazines
  • Phthalazines
  • Neoplasm Transplantation
  • Muscle Neoplasms
  • Male
  • K562 Cells