Upregulation of CD44 expression by interleukins 1, 4, and 13, transforming growth factor-beta1, estrogen, and progestogen in human cervical adenocarcinoma cell lines.
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)-1alpha, IL-1beta, IL-4, IL-13, transforming growth factor (TGF)-beta1, 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-1alpha, IL-1beta, IL-4, IL-13, TGF-beta1 (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.
Ibrahim
E M
EM
Division of Clinical Science, Section of Obstetrics and Gynaecology and Division of Oncology and Cellular Pathology, University of Sheffield, UK. emibrahim@hotmail.com
Stewart
R L
RL
Corke
K
K
Blackett
A D
AD
Tidy
J A
JA
Wells
M
M
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
D004967:Estrogens; D018960:Hyaluronan Receptors; D007375:Interleukin-1; D018793:Interleukin-13; D007378:Interleukins; D011372:Progestins; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D015847:Interleukin-4