Zika Virus Selectively Kills Aggressive Human Embryonal CNS Tumor Cells In Vitro and In Vivo

Author(s):Show less -

Kaid, Carolini ^[1] ; Goulart, Ernesto ^[1] ; Caires-Junior, Luiz C. ^[1] ; Araujo, Bruno H. S. ^[2] ; Soares-Schanoski, Alessandra ^[3] ; Bueno, Heloisa M. S. ^[1] ; Telles-Silva, Kayque A. ^[1] ; Astray, Renato M. ^[3] ; Assoni, Amanda F. ^[1] ; Junior, Antonio F. R. ^[1] ; Ventini, Daniella C. ^[3] ; Puglia, Ana L. P. ^[3] ; Gomes, Roselane P. ^[3] ; Zatz, Mayana ^[1] ; Okamoto, Oswaldo K. ^[1]

Affiliation

^[1] Univ Sao Paulo, Human Genome & Stem Cell Res Ctr, Biosci Inst, Dept Genet & Evolutionary Biol, Sao Paulo, SP - Brazil

^[2] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, Campinas, SP - Brazil

^[3] Butantan Inst, Sao Paulo - Brazil

• Document type: Journal article
• Source: Cancer Research; v. 78, n. 12, p. 3363-3374, JUN 15 2018.
• Web of Science Citations: 6

Abstract

Zika virus (ZIKV) is largely known for causing brain abnormalities due to its ability to infect neural progenitor stem cells during early development. Here, we show that ZIKV is also capable of infecting and destroying stem-like cancer cells from aggressive human embryonal tumors of the central nervous system (CNS). When evaluating the oncolytic properties of Brazilian Zika virus strain (ZIKV(BR)) against human breast, prostate, colorectal, and embryonal CNS tumor cell lines, we verified a selective infection of CNS tumor cells followed by massive tumor cell death. ZIKV(BR) was more efficient in destroying embryonal CNS tumorspheres than normal stem cell neurospheres. A single intracerebroventricular injection of ZIKV(BR) in BALB/c nude mice bearing orthotopic human embryonal CNS tumor xenografts resulted in a significantly longer survival, decreased tumor burden, fewer metastasis, and complete remission in some animals. Tumor cells closely resembling neural stem cells at the molecular level with activated Wnt signaling were more susceptible to the oncolytic effects of ZIKV(BR). furthermore, modulation of Wnt signaling pathway significantly affected ZIKV(BR)-induced tumor cell death and viral shedding. Altogether, these preclinical findings indicate that ZIKV(BR) could be an efficient agent to treat aggressive forms of embryonal CNS tumors and could provide mechanistic insights regarding its oncolytic effects. Significance: Brazilian Zika virus strain kills aggressive metastatic forms of human CNS tumors and could be a potential oncolytic agent for cancer therapy. (C) 2018 AACR (AU)

• FAPESP's process: 16/09707-8 - Interaction between the protein VAPB and the development of embryonic tumors on the central nervous system
• Grantee: Amanda Faria Assoni
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/16283-2 - Development of tissue bioengineering techniques for the functional reconstruction of ex vivo iPSC cell livers
• Grantee: Luiz Carlos de Caires Júnior
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/08049-1 - The role of astrocytes in the synaptic plasticity of neurons derived from induced pluripotent stem cells from Down Syndrome patients
• Grantee: Bruno Henrique Silva Araujo Torres
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/14821-1 - Development of functional hepatic by-pass using iPSCs-derived cells
• Grantee: Ernesto da Silveira Goulart Guimarães
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC