Abstract

Although cervical adenocarcinoma constitutes approximately 10–20% of primary malignant tumors of the uterine cervix, its pathogenesis is less well understood than that of the corresponding squamous cancer. CD44 is a cell surface glycoprotein postulated to play a role in many biologic processes including tumor growth and metastasis. We have previously reported from immunohistochemical studies that a particular CD44 variant (CD44v5) is consistently overexpressed in endocervical neoplasia. It thus has potential as a diagnostic marker and even as a target for therapeutic approaches directed against specific epitopes. The aim of this study was to investigate which cytokines and hormones are capable of modulating CD44v5 expression, using a cell culture model. The effects of interleukin (IL)-1α, IL-1β, IL-4, IL-13, transforming growth factor (TGF)-β1, estrogen, and progestogen on CD44v5 expression were examined in cultures of three human cervical adenocarcinoma cell lines (HeLa, HeLa229, and HS588T). Expression was assessed using dual fluorescence-labeled flow cytometry and western blotting techniques. It was found that incubation of cultures for 72 h with IL-1α, IL-1β, IL-4, IL-13, TGF-β1 (all at 0.1–10 ng/mL), estrogen (5–10 ng/mL), or progestogen (5–20 ng/mL) induced significant upregulation of CD44v5. These factors are likely to exert a similar stimulatory influence in vivo and may contribute to the process of carcinogenesis.