Human papillomavirus-16-E7 oncoprotein enhances the expression of adhesion molecules in cervical endothelial cells but not in human umbilical vein endothelial cells.
OBJECTIVE
E7 is one of the oncoproteins encoded by human papillomavirus-16 (HPV-16), the major etiologic factor responsible for cervical cancer. Human papillomavirus-16-E7 expressed by human uterine cervix carcinoma cells is also released in the extracellular compartment where it induces immune suppression. We investigated whether E7 was also responsible for the enhanced endothelial adhesiveness required in cancer progression.


METHODS
We treated cervical microvascular endothelial cells (CrMVEn) and human umbilical vein endothelial cells (HUVEC) with E7, tumor necrosis factor-alpha (TNF-alpha), and hydrogen peroxide (H2O2) and measured the expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) by fluorescent-activated cell sorter analysis.


RESULTS
E7 strongly induced the expression of E-selectin, ICAM-1, and VCAM-1 in CrMVEn, but not in HUVEC. Tumor necrosis factor-alpha further increased the endothelial expression of adhesion molecules in CrMVEn. Hydrogen peroxide pre-treatment resulted in an enhanced ICAM-1 and a decreased E-selectin and VCAM-1 expression. We also show indirect effects when endothelial cells were stimulated with the supernatant of E7-pretreated macrophages.


CONCLUSIONS
These results show that HPV-16-E7 oncoprotein strongly induces adhesion molecules expression in organ-specific endothelial cells.
D'Anna
R
R
Laboratoire de Physiologie Cellulaire, Université Pierre et Marie Curie, Paris, France.
Le Buanec
H
H
Bizzini
B
B
Burny
A
A
Giannouli
C
C
Zagury
J F
JF
Gallo
R C
RC
Zagury
D
D
D'Alessio
P
P
D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology*; D019040:E-Selectin / Q000378:metabolism; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D009856:Oncogene Proteins, Viral / Q000494:pharmacology*; D027383:Papillomaviridae; D050725:Papillomavirus E7 Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins; D002583:Uterine Cervical Neoplasms / Q000503:physiopathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C059731:oncogene protein E7, Human papillomavirus type 16; D018799:Intercellular Adhesion Molecule-1; D006861:Hydrogen Peroxide