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Journal of Medical Oncology and Therapeutics | Volume: 3
July 23-25, 2018 | Moscow, Russia
12
th
World Cancer Congress
Overexpression of HIV-1 reverse transcriptase increases tumorigenic and metastatic activity of
Malignant cells
Elizaveta Starodubova*
2,3
, Pankova E
1,2
, Gordeychuk I
1,3,4
, Petkov S
3
, Jansons J
5,6
, Podschwadt P
3
, Mezale D
5
, Fridrihsone I
5
, Skrastina D
6
,
Abakumov M
1
, Tukhvatulin A
1
, Strumfa I
5
and
Isaguliants M
1,3,4,5
1
Gamaleja Research Center of Epidemiology and Microbiology, Russia
2
Engelhardt Institute of Molecular Biology, Russia
3
Karolinska Institutet, Sweden
4
Russian Academy of Sciences, Russia
5
Riga Stradins University, Latvia
6
Biomedical Research and Study Center, Latvia
H
IV-1 infection is often accompanied by oncological
complications attributed to immune suppression, and
angiogenic and/or directly oncogenic properties of HIV Tat,
Nef and p17. Here, we studied oncogenicity of HIV-1 reverse
transcriptase (RT). Panel of murine adenocarcinoma 4T1luc2
(Perkin Elmer, USA) subclones stably expressing consensus
HIV-1 FSU_A RT or its variants with primary mutations of
resistance to nucleoside (RT_An) or non-nucleoside inhibitors
(RT_Ann) common in the territory of former USSR
1
, was
generated by lentiviral transduction of 4T1luc2 cells. Parental
4T1luc2; 4T1luc2RT (multiplicity of infection/MOI 1, 5, 20);
4T1luc2RT_An, and 4T1luc2RT_Ann subclones (MOI10)
were subcutaneously implanted into BALB/c mice. Tumor
growth was monitored by morphologic measurements and
bioluminescence imaging (BLI; Perkin Elmer). After three
weeks, mice were sacrificed, tumors and organs were excised,
subjected to ex vivo BLI, then dehydrated, paraffin-embedded
and sectioned. Number of metastatic cells was assessed by BLI
and in parallel, quantified on haematoxylin-eosin-stained slides
by computer-assisted morphometry (NIS-Elements software,
Nikon, Japan). Splenocytes were isolated, stimulated with RT-
derived peptides, and IFN-Ὑ/IL-2 secretion was assessed by
Fluorospot (Mabtech, Sweden). Within 10 days, all subclones
formed palpable tumors. 4T1luc2RT-tumors grew faster than
those formed by 4T1luc2, or 4T1luc2RT_An, or 4T1luc2RT_
Ann cells (p<0,05). 4T1luc2RT tumor-bearing mice had more
metastasis in lungs and liver than mice implanted with 4T1luc2
cells. Drug-resistance mutations decreased metastatic activity
of 4T1luc2RT_An and 4T1luc2RT_Ann subclones below that
of parental 4T1luc2 cells (p<0,05). Expression of RTs induced
no immune response. Thus, expression of nonmutated RT
increases tumorigenic and metastatic activity of malignant
cells. Supported by RFBR#17_54_30002, and 17_04_00583.
Speaker Biography
Elizaveta Starodubova has completed her PhD in the Engelhardt Institute of
Molecular Biology, Russian Academy of Sciences, and continued her postdoctoral
studies there and at the Department of Microbiology, Tumor and Cell Biology (MTC),
Karolinska Institutet, Stockholm. She performs her studies in the field of antigen
processing and design of prototype DNA-vaccines against viral infections and cancer.
e:
estarodubova@gmail.com