Characterizing the Inflammatory Microenvironment in K14-HPV16 Transgenic Mice: Mast Cell Infiltration and MicroRNA Expression

被引：4

作者：

Costa, Alexandra C. ^{[1
,2
,3
]}

Santos, Joana M. O. ^{[1
,2
]}

Medeiros-Fonseca, Beatriz ^{[4
]}

Oliveira, Paula A. ^{[4
]}

Bastos, Margarida M. S. M. ^{[5
,6
]}

Brito, Haissa O. ^{[7
,8
]}

da Costa, Rui M. Gil ^{[1
,4
,5
,6
,7
,8
]}

Medeiros, Rui ^{[1
,2
,3
,9
,10
]}

机构：

[1] Porto Comprehens Canc Ctr PortoCCC, Portuguese Oncol Inst Porto IPO Porto, Res Ctr IPO Porto CI IPOP RISE CI IPOP Hlth Res N, Mol Oncol & Viral Pathol Grp, P-4200072 Porto, Portugal

[2] Univ Porto FMUP, Fac Med, P-4200319 Porto, Portugal

[3] Reg Nucleus North Liga Portuguesa Canc Nucleo Reg, Res Dept Portuguese League Canc, P-4200177 Porto, Portugal

[4] Univ Tras Os Montes & Alto Douro UTAD, Ctr Res & Technol Agroenvironm & Biol Sci CITAB, Inov4Agro, P-5000801 Vila Real, Portugal

[5] Univ Porto, Fac Engn, LEPABE Lab Proc Engn Environm Biotechnol & Energy, Rua Dr Roberto Frias, P-4200465 Porto, Portugal

[6] Univ Porto, Fac Engn, ALiCE Associate Lab Chem Engn, Rua Dr Roberto Frias, P-4200465 Porto, Portugal

[7] Fed Univ Maranhao UFMA, Dept Morphol, Postgrad Programme Adult Hlth PPGSAD, BR-65080805 Sao Luis, Maranhao, Brazil

[8] UFMA Univ Hosp HUUFMA, BR-65080805 Sao Luis, Maranhao, Brazil

[9] Portuguese Oncol Inst Porto IPO Porto, Virol Serv, P-4200072 Porto, Portugal

[10] Fernando Pessoa Univ, Biomed Res Ctr CEBIMED, Fac Hlth Sci, P-4249004 Porto, Portugal

来源：

CANCERS | 2022年 / 14卷 / 09期

关键词：

HPV16; inflammation; mast cells; K14-HPV16; microRNAs; cancer; carcinogenesis; IMMUNE CONTEXTURE; CANCER; ROLES; CARCINOGENESIS; MIRNAS; DYSREGULATION; PROGRESSION; PREDICTION; PROGNOSIS; APOPTOSIS;

D O I：

10.3390/cancers14092216

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Simple Summary K14-HPV16 transgenic mice have proved to be a useful model to study the carcinogenic cascade induced by HPV16, the tumor microenvironment and also the epigenetic and genetic factors associated with this type of malignancy. The aim of our study was to evaluate the infiltration of mast cells in two cutaneous regions with different severity of the lesions and to identify potential microRNAs that may regulate mast cell infiltration in this model. We were able to confirm that increased mast cell infiltration is associated with progression of HPV-induced lesions, and that miR-223-3p and miR-125b-5p might be assisting this process via the regulation of mast cell chemotactic proteins. 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(-Delta Delta Ct) = 2.09) and miR-223-3p (p = 0.013, 2(-Delta Delta Ct) = 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.

引用

页数：18