Inflammation is a critical component of tumorigenesis. Tumor microenvironment participates in the neoplastic process fostering proliferation, survival and migration. Virus-induced tumors, like HPV-induced Squamous Cell Carcinomas, represent a paradigmatic example of the interplay between inflammation, as integral part of the innate antiviral response, and malignant transformation. To study the tumorigenic role of inflammatory mediators in HPV + cells, we analyzed by real time RT-PCR the expression of selected inflammatory cytokines, chemokines and related molecules in human foreskin keratinocytes transduced by E6 and E7 from mucosalHPV-16 (K16) or cutaneousHPV-38 (K38) genotypes comparing them to primary Human Foreskin Keratinocytes. We also performed silencing experiments by using E6/E7 siRNA in HPV + SiHa carcinoma cells to verify the involvement of the viral proteins. IL-1? and IL-1? mRNAs are downregulated in K16 and K38 cells, whereas IL-1R1 mRNA level is comparable in all cell lines. IL-6 mRNA level is unchanged in K16 and downregulated in K38. E6/E7 silencing in SiHa confirms the effect specificity. MIP-3?, CCL-17 and CCl-22 mRNA levels in K16 cells are also deregulated. Deregulation of MIP-3? mRNA appears to be related to miR-21 over-expression detected in both K16 and K38. The effect of the IFN-? on the levels of these pro-inflammatory mediators will be also discussed. Experiments on paraffin embedded tissues are in progress to verify MIP-3? deregulation in vivo. Our results suggest that HPV is able to modify the tumor microenvironment through the synthesis and release of specific pro-inflammatory cytokines and chemokines possibly to interfere with the leucocytes trafficking and/or allowing a better tumor growth and infiltration.
Pro-inflammatory cytokines and chemokines in HPV-positive cancer cells
Fiorucci Gianna;
2015
Abstract
Inflammation is a critical component of tumorigenesis. Tumor microenvironment participates in the neoplastic process fostering proliferation, survival and migration. Virus-induced tumors, like HPV-induced Squamous Cell Carcinomas, represent a paradigmatic example of the interplay between inflammation, as integral part of the innate antiviral response, and malignant transformation. To study the tumorigenic role of inflammatory mediators in HPV + cells, we analyzed by real time RT-PCR the expression of selected inflammatory cytokines, chemokines and related molecules in human foreskin keratinocytes transduced by E6 and E7 from mucosalHPV-16 (K16) or cutaneousHPV-38 (K38) genotypes comparing them to primary Human Foreskin Keratinocytes. We also performed silencing experiments by using E6/E7 siRNA in HPV + SiHa carcinoma cells to verify the involvement of the viral proteins. IL-1? and IL-1? mRNAs are downregulated in K16 and K38 cells, whereas IL-1R1 mRNA level is comparable in all cell lines. IL-6 mRNA level is unchanged in K16 and downregulated in K38. E6/E7 silencing in SiHa confirms the effect specificity. MIP-3?, CCL-17 and CCl-22 mRNA levels in K16 cells are also deregulated. Deregulation of MIP-3? mRNA appears to be related to miR-21 over-expression detected in both K16 and K38. The effect of the IFN-? on the levels of these pro-inflammatory mediators will be also discussed. Experiments on paraffin embedded tissues are in progress to verify MIP-3? deregulation in vivo. Our results suggest that HPV is able to modify the tumor microenvironment through the synthesis and release of specific pro-inflammatory cytokines and chemokines possibly to interfere with the leucocytes trafficking and/or allowing a better tumor growth and infiltration.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
