ID: 109: Pro-inflammatory cytokines and chemokines in HPV-positive cancer cells

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• 作者：Giorgio Mangino¹ ; Maria Simona Zangrillo¹ ; Maria Vincenza Chiantore² ; Marco Iuliano¹ ; Rosita Accardi³ ; Massimo Tommasino³ ; Gianna Fiorucci⁴ ; Giovanna Romeo¹ ; ² ; ⁴ ;
• 刊名：Cytokine
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：76
• 期：1
• 页码：86
• 全文大小：45 K

文摘

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-1α and IL-1β 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-3α, CCL-17 and CCl-22 mRNA levels in K16 cells are also deregulated.

Deregulation of MIP-3α mRNA appears to be related to miR-21 over-expression detected in both K16 and K38. The effect of the IFN-β on the levels of these pro-inflammatory mediators will be also discussed. Experiments on paraffin embedded tissues are in progress to verify MIP-3α 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.