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Updated: Sep 23, 2025
Characterization of Immune Cells and Proinflammatory Mediators in the Pulmonary Environment
Published on: June 24, 2020
Characterizing the Inflammatory Microenvironment in K14-HPV16 Transgenic Mice: Mast Cell Infiltration and MicroRNA
Alexandra C Costa1,2,3, Joana M O Santos1,2, Beatriz Medeiros-Fonseca4
1Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal.
Abstract:
High-risk human papillomavirus (HPV) is the etiologic agent of several types of cancer. Mast cells’ role as either a driving or opposing force for cancer progression remains controversial. MicroRNAs are dysregulated in several HPV-induced cancers, and can influence mast cell biology. The aim of this study was to evaluate mast cell infiltration and to identify microRNAs potentially regulating this process. Transgenic male mice (K14-HPV16; HPV+) and matched wild-type mice (HPV−) received 7,12-Dimethylbenz[a]anthracene (DMBA) (or vehicle) over 17 weeks. Following euthanasia, chest skin and ear tissue samples were collected. Mast cell infiltration was evaluated by immunohistochemistry. MicroRNAs associated with mast cell infiltration were identified using bioinformatic tools. MicroRNA and mRNA relative expression was evaluated by RT-qPCR. Immunohistochemistry showed increased mast cell infiltration in HPV+ mice (p < 0.001). DMBA did not have any statistically significant influence on this distribution. Ear tissue of HPV+ mice showed increased mast cell infiltration (p < 0.01) when compared with chest skin samples. Additionally, reduced relative expression of miR-125b-5p (p = 0.008, 2−ΔΔCt = 2.09) and miR-223-3p (p = 0.013, 2−ΔΔCt = 4.42) seems to be associated with mast cell infiltration and increased expression of target gene Cxcl10. These results indicate that HPV16 may increase mast cell infiltration by down-regulating miR-223-3p and miR-125b-5p.
Insights
High-risk human papillomavirus (HPV) infection increases mast cell infiltration in mice. This process may involve the down-regulation of specific microRNAs, miR-223-3p and miR-125b-5p, suggesting a novel regulatory mechanism in HPV-driven carcinogenesis.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- High-risk human papillomavirus (HPV) is linked to various cancers.
- The role of mast cells in cancer progression is debated.
- MicroRNAs (miRNAs) are implicated in HPV-induced cancers and mast cell biology.
Purpose of the Study:
- To investigate mast cell infiltration in HPV-induced carcinogenesis.
- To identify specific microRNAs regulating mast cell infiltration in HPV-positive models.
Main Methods:
- Utilized K14-HPV16 transgenic mice and wild-type littermates.
- Administered 7,12-Dimethylbenz[a]anthracene (DMBA) or vehicle over 17 weeks.
- Assessed mast cell infiltration via immunohistochemistry and miRNA/mRNA expression via RT-qPCR.
Main Results:
- HPV16-positive mice exhibited significantly increased mast cell infiltration compared to controls (p < 0.001).
- DMBA treatment did not significantly alter mast cell distribution.
- Reduced expression of miR-125b-5p and miR-223-3p correlated with mast cell infiltration and increased Cxcl10 expression.
Conclusions:
- HPV16 infection promotes mast cell infiltration in mouse skin.
- Down-regulation of miR-223-3p and miR-125b-5p may mediate HPV-driven mast cell recruitment.
- These findings suggest a potential miRNA-mediated mechanism in HPV-associated cancer development.
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