Darlene Dixon

Tobacco Smoke Condensate Induces Morphologic Changes in Human Papillomavirus-Positive Cervical Epithelial Cells Consistent with Epithelial to Mesenchymal Transition (EMT) with Activation of Receptor Tyrosine Kinases and Regulation of TGFB

High-risk human papillomavirus (HR-HPV; HPV-16) and cigarette smoking are associated with cervical cancer (CC); however, the underlying mechanism(s) remain unclear. Additionally, the carcinogenic components of tobacco have been found in the cervical mucus of women smokers. Here, we determined the effects of cigarette smoke condensate (CSC; 3R4F) on human ectocervical cells (HPV-16 Ect/E6E7) exposed to CSC at various concentrations (10−6–100 μg/mL). We found CSC (10−3 or 10 μg/mL)-induced proliferation, enhanced migration, and histologic and electron microscopic changes consistent with EMT in ectocervical cells with a significant reduction in E-cadherin and an increase in the vimentin expression compared to controls at 72 h. There was increased phosphorylation of receptor tyrosine kinases (RTKs), including Eph receptors, FGFR, PDGFRA/B, and DDR2, with downstream Ras/MAPK/ERK1/2 activation and upregulation of common EMT-related genes, TGFB SNAI2, PDGFRB, and SMAD2. Our study demonstrated that CSC induces EMT in ectocervical cells with the upregulation of EMT-related genes, expression of protein biomarkers, and activation of RTKs that regulate TGFB expression, and other EMT-related genes. Understanding the molecular pathways and environmental factors that initiate EMT in ectocervical cells will help delineate molecular targets for intervention and define the role of EMT in the initiation and progression of cervical intraepithelial neoplasia and CC.

Nonproliferative and Proliferative Lesions of the Rat and Mouse Female Reproductive System: Revised INHAND Terms for Ovarian Sex Cord/Stromal Lesions

The nomenclature for the female reproductive system was originally published in 2014. After 10 years of practical use, the scientific community requested from the organ working group (OWG) a review of the terminology and criteria for diagnosing ovarian sex cord/stromal lesions. As a result, OWG proposes the use of “sex cord/stromal” as the base terminology for hyperplasia and tumors to better reflect their origin from the sex cord/stroma and make the terminology internally consistent. When no predominant cell type is present, these lesions should then be designated as mixed cell type (e.g., “hyperplasia, sex cord/stromal, mixed,” or “tumor, sex cord/stromal, mixed, benign”). When a clear, predominate cell type is present, the diagnosis should indicate that cell type (e.g., “sex cord/stromal, granulosa cell” or “sex cord/stromal, theca cell”). In the case of tumors, benign or malignant would be applied as appropriate. With these diagnostic revisions, the OWG for the female reproductive system attempts to provide clarification and refinement of criteria to be used for sex cord/stromal lesions.