Role of heat-shock proteins in infection of human adenocarcinoma cell line MCF-7 by tumor-adapted rotavirus isolates
Abstract
Background:Viruses are being used as alternative and complementary tools for treating cancers. Oncolytic viruses exhibit tumor tropism, ability to enhance anti-tumor immunity and ability to be used in combination with conventional chemotherapy and radiotherapy. We have recently selected some rotavirus isolates which are adapted to efficiently infect and kill tumor cell lines.
Aim:We tested five tumor cell-adapted rotavirus isolates for their ability to infect the human adenocarcinoma cell line MCF-7.
Methods:Cell surface membrane-associated proteins mediating virus particle attachment were characterized using ELISA, immunoprecipitation, FACS analysis, and antibody blocking.
Results:It was found that heat shock proteins (HSPs) such as Hsp90, Hsp70, Hsp60, and Hsp40 are expressed on the cell surface forming complexes with protein disulfide isomerase (PDI), integrin β3, and heat shock cognate protein 70 (Hsc70) in lipid raft microdomains. Interaction of rotavirus isolates with these cellular proteins was further confirmed by a competition assay and an inhibition assay involving the HSPs tested.
Conclusion:Our findings suggest that the tumor cell-adapted rotavirus isolates studied here offer a promising tool for killing tumor cells, thus encouraging further research into this topic, including animal models.
Authors
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Keywords
- Oncolytic Viruses
- Oncolytic Virotherapy
- Rotavirus
- Cancer Vaccines
- MCF-7 Cells
- Protein Disulfide-Isomerases
- Proto-Oncogene Proteins c-akt
- Heat-Shock Proteins
- Rotavirus Infections
- Integrins
- Pyroptosis
- Autophagic Cell Death
Author Biographies
, Universidad Nacional de Colombia, Faculty of Medicine, Department of Physiological Sciences, Bogota, D.C., Colombia
https://orcid.org/0000-0001-8206-6174
, Universidad Nacional de Colombia, Faculty of Medicine, Department of Physiological Sciences, Bogota, D.C., Colombia
Biologist from the Universidad del Atlantico, student of the Master's Degree in Biochemistry at the Faculty of Medicine of the Universidad Nacional de Colombia. His thesis work as a partial requirement to obtain the title of MASTER IN BIOCHEMISTRY was entitled: "INTERACTION OF HSP90, HSP70, HSP60 AND HSP40 WITH THE HSC70, PDI, INTEGRIN Β3 PROTEINS AND WITH ROTAVIRUS IN THE CYTOPLASMA MEMBRANE OF TUMOR CELLS". It was completed in its entirety. It had already been evaluated and prepared to support it when, unfortunately, he died in Bogotá. Although it is difficult to know what the jury would think that would evaluate him, due to the quality of the experiments and the importance of the results, surely the work not only gave him to graduate without setbacks, but he deserved one more award, for example, "thesis meritorious.” The results of his work were published in three journals of international impact and bear his name. The National University granted him the Post-mortem degree with the title of Magister in Biochemistry.
, Universidad Nacional de Colombia, Faculty of Medicine, Department of Physiological Sciences, Bogota, D.C., Colombia
https://orcid.org/0000-0003-2863-6345
MD, MSc, Ph.D. Doctor graduated from the Universidad del Valle, Professor of the Faculty of Medicine of the Universidad Nacional de Colombia. He is a researcher in rotavirus since his doctoral studies in 2000. Coordinator of the Molecular Biology of viruses laboratory of the Department of Physiological Sciences. His published works are related to the cellular receptors that rotaviruses use to enter the cell and drugs that inhibit the infectious process. Likewise, the use of rotavirus as a possible agent in the fight against cancer (oncolytic virus), focusing on describing the receptors that the virus uses to enter the tumor cell, explains the infectious specificity and non-entry non-tumor cells. He is currently investigating how to transport the oncolytic virus to reach the tumor cell without being blocked by the antibodies that patients have since they have antibodies against rotavirus since childhood.
, Universidad Nacional de Colombia, Faculty of Medicine, Department of Physiological Sciences, Bogota, D.C., Colombia
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