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Photon-induced cell migration and integrin expression promoted by DNA integration of HPV16 genome.
- Source :
-
Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] [Strahlenther Onkol] 2014 Oct; Vol. 190 (10), pp. 944-9. Date of Electronic Publication: 2014 Mar 19. - Publication Year :
- 2014
-
Abstract
- Background: Persistent human papilloma virus 16 (HPV16) infections are a major cause of cervical cancer. The integration of the viral DNA into the host genome causes E2 gene disruption which prevents apoptosis and increases host cell motility. In cervical cancer patients, survival is limited by local infiltration and systemic dissemination. Surgical control rates are poor in cases of parametrial infiltration. In these patients, radiotherapy (RT) is administered to enhance local control. However, photon irradiation itself has been reported to increase cell motility. In cases of E2-disrupted cervical cancers, this phenomon would impose an additional risk of enhanced tumor cell motility. Here, we analyze mechanisms underlying photon-increased migration in keratinocytes with differential E2 gene status.<br />Methods: Isogenic W12 (intact E2 gene status) and S12 (disrupted E2 gene status) keratinocytes were analyzed in fibronectin-based and serum-stimulated migration experiments following single photon doses of 0, 2, and 10 Gy. Quantitative FACS analyses of integrin expression were performed.<br />Results: Migration and adhesion are increased in E2 gene-disrupted keratinocytes. E2 gene disruption promotes attractability by serum components, therefore, effectuating the risk of local infiltration and systemic dissemination. In S12 cells, migration is further increased by photon RT which leads to enhanced expression of fibronectin receptor integrins.<br />Conclusion: HPV16-associated E2 gene disruption is a main predictor of treatment-refractory cancer virulence. E2 gene disruption promotes cell motility. Following photon RT, E2-disrupted tumors bear the risk of integrin-related infiltration and dissemination.
- Subjects :
- Cell Line
Cell Movement radiation effects
Dose-Response Relationship, Drug
Dose-Response Relationship, Radiation
Keratinocytes radiation effects
Photons
Promoter Regions, Genetic genetics
Promoter Regions, Genetic radiation effects
Radiation Dosage
Transfection methods
Virus Integration genetics
Cell Movement physiology
DNA, Viral genetics
DNA-Binding Proteins genetics
Genome, Viral genetics
Human papillomavirus 16 genetics
Integrins metabolism
Keratinocytes physiology
Oncogene Proteins, Viral genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1439-099X
- Volume :
- 190
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]
- Publication Type :
- Academic Journal
- Accession number :
- 24643883
- Full Text :
- https://doi.org/10.1007/s00066-014-0649-6