Toll-like receptor transcriptome in the HPV-positive cervical cancer microenvironment.
The human papillomavirus (HPV) directly infects cervical keratinocytes and interferes with TLR signalling. To shed light on the effect of HPV on upstream receptors, we evaluated TLRs 1-9 gene expression in HPV-negative normal and HPV-positive pre-malignant and malignant ex vivo cervical tissue. Quantitative real-time polymerase chain reaction was performed separately for epithelial and stromal tissue compartments. Differences in gene expression were analyzed by the Jonckheere-Terpstra trend test or the Student's t-test for pairwise comparison. Laser capture microdissection revealed an increase in TLR3 and a decrease in TLR1 mRNA levels in dysplastic and carcinoma epithelium, respectively. In the stroma, a trend of increasing TLR 1, 2, 5, 6, and 9 mRNA levels with disease severity was found. These findings implicate the involvement of TLR3 and TLR1 in early and late cervical carcinogenesis, respectively, suggesting that stromal upregulation of TLRs may play a role in cervical disease progression.
Probe Development and Biomarker Exploration Thunder Bay Regional Research Institute, Thunder Bay, ON, Canada P7B 6V4.
Correne A
CA
DeCarlo
Bruce
B
Rosa
Robert
R
Jackson
Sarah
S
Niccoli
Nicholas G
NG
Escott
Ingeborg
I
Zehbe
D002277:Carcinoma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology; D002472:Cell Transformation, Viral / Q000276:immunology; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000473:pathology; D018450:Disease Progression; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D052162:Human papillomavirus 16 / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D006965:Hyperplasia; D007113:Immunity, Innate; D030361:Papillomavirus Infections / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D011230:Precancerous Conditions / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D059016:Tumor Microenvironment; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology
D051193:Toll-Like Receptors