ISSN 2312-3672
Kurmyshkina O., Belova L., Kovchur P., Volkova T. VEGF-associated factors and regulatory T-cells in the context of neoangiogenesis in cervical cancer of 0-IA stages // Journal of Biomedical Technologies. 2015. № 1. P. 1‒8. DOI: 10.15393/j6.art.2015.3343
Issue № 1 (2015)
Original research
VEGF-associated factors and regulatory T-cells in the context of neoangiogenesis in cervical cancer of 0-IA stages
| Kurmyshkina Olga Vadimovna | Petrozavodsk State University, 33 Lenin str., Petrozavodsk, Russia, studioza@mail.ru |
| Belova Lubava Leonidovna | Petrozavodsk State University, 33 Lenin str., Petrozavodsk, Russia, lubavushko@gmail.com |
| Kovchur Pavel Ivanovich | Petrozavodsk State University, 33 Lenin str., Petrozavodsk, Russia, pkovchur@mail.ru |
| Volkova Tatyana Olegovna | Petrozavodsk State University, 33 Lenin str., Petrozavodsk, Russia, VolkovaTO@yandex.ru |
|
cervical cancer neoangiogenesis vascular endothelial growth factors regulatory T-cells transforming growth factor gene expression |
Investigation of molecular factors and mechanisms, controlling the processes of lymphangiogenesis, invasion and metastasis in cervical cancer, represents one of the most urgent tasks of molecular oncogynecology. Lymphangiogenesis-promoting signals may come from either tumor cells or specific subpopulations of immune cells. In this connection, our aim was to explore the changes of expression levels of VEGF-C, VEGF-R3, PlGF, and ETS1 genes in samples of pre- and microinvasive squamous cervical cancer, compared to normal epithelium of the cervix, and to determine deviations in regulatory T-cells (Tregs) counts and TGF plasma level in cervical cancer patients relative to the control group of healthy donors.
Methods. Tissues biopsies and peripheral blood samples were obtained from patients of the Republic Oncological Dispensary. Real-time PCR was used to analyze gene expression. Immunophenotyping of blood lymphocytes was done by means of multi-color flow cytometry. The level of TGF1 was assessed by ELISA.
Results. 1. Significant increase of VEGF-C, VEGF-R3, PlGF, and ETS1 gene expression in cervical cancer samples, as compared to normal epithelium, was found, however, the total profile of activity of these genes was shown to be specific for each case. These results indicate very early establishment of lymphangiogenic microenvironment in cervical cancer locus – at the stage of preinvasive growth. 2. The number of circulating Tregs described by phenotype CD4(+)CD25(+/high)CD127(dim/neg)FoxP3(+) was analyzed. Elevated counts of Tregs were revealed in women with stage 0-IA cervical cancer, compared to healthy controls; increase of Treg numbers was accompanied by significant elevation of TGF1 concentration in plasma.
Conclusion. Cervical cancer patients at initial stages of tumor progression demonstrate coordinated changes of the parameters chosen for our study, both at local and systemic level; these changes are likely to drive stimulation of lymphangiogenesis and to form environment for tumor cell invasion and early metastasis. |
Displays: 3871; Downloads: 7030;