---
OA_type: closed access
_id: '3932'
abstract:
- lang: eng
text: 'OBJECTIVES: The EGFR is expressed in malignant ovarian tumor tissue, and
tissue content of EGFR has been directly associated with poor prognosis in patients
with ovarian cancer. The uPA system plays a role in pericellular proteolysis,
cell migration, invasion, and is over-expressed in ovarian cancer. This study
explored the effects of EGF on uPAR expression in the ovarian cancer cell line
OVCAR-3. METHODS: We used OVCAR-3 cells and the following methods: cell migration
assay, time-lapse video microscopy, real-time PCR, assays for cellular binding
of 125I-uPA and cellular degradation of 125I-uPA:PAI-1 complex, biosynthetic labeling
using 35S-methionin, Western blot, Northern blot, and ELISAs for uPA, PAI-1, and
uPAR. RESULTS: EGF up-regulates both protein and mRNA not only for uPAR, but also
for the ligand uPA and its inhibitor PAI-1. Cell surface uPAR, in control as well
as EGF-stimulated cells, is present only in the intact, not the cleaved, form.
Ligand binding experiments showed an increase of endogenously occupied uPAR, whereas
non-occupied receptor sites were not increased. In addition, EGF treatment resulted
in decreased degradation of radiolabeled uPA:PAI-1 complex. This suggests decreased
internalization of uPAR, since the complex is internalized together with uPAR.
Like EGF, colchicine, which inhibits endocytosis, increased cell surface expression
of uPAR. In addition, we found an immediate increase of uPAR after exposing the
cells to EGF and this was accompanied by a transient increase of cell migration.
The increase of cell surface uPAR in response to EGF is accompanied by increased
release of the soluble form of uPAR (suPAR) to the medium as well as by increased
cell migration. Both uPAR and suPAR increased in cells treated with the endocytosis
inhibitor colchicine even though cell migration was inhibited, suggesting that
the mechanism of uPAR shedding is not related to cell migration. CONCLUSION: Increased
cell surface uPAR in response to EGF stimulation results from mobilization of
uPAR from detergent-resistant domains, increased expression of uPAR mRNA, and
decreased internalization and degradation of uPAR. Both the anti-uPAR antibody
R3, which inhibits binding of uPA, and the EGFR phosphorylation inhibitor Iressa
inhibited cell migration in response to uPA as well as to EGF, suggesting that
EGFR and uPAR are engaged in the same multiprotein assembly on the cell surface.'
article_processing_charge: No
article_type: original
author:
- first_name: Emir
full_name: Henic, Emir
last_name: Henic
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
- first_name: Stefan
full_name: Hansson, Stefan
last_name: Hansson
- first_name: Gunilla
full_name: Høyer Hansen, Gunilla
last_name: Høyer Hansen
- first_name: Bertil
full_name: Casslén, Bertil
last_name: Casslén
citation:
ama: Henic E, Sixt MK, Hansson S, Høyer Hansen G, Casslén B. EGF-stimulated migration
in ovarian cancer cells is associated with decreased internalization, increased
surface expression, and increased shedding of the urokinase plasminogen activator
receptor. Gynecologic Oncology. 2006;101(1):28-39. doi:10.1016/j.ygyno.2005.09.038
apa: Henic, E., Sixt, M. K., Hansson, S., Høyer Hansen, G., & Casslén, B. (2006).
EGF-stimulated migration in ovarian cancer cells is associated with decreased
internalization, increased surface expression, and increased shedding of the urokinase
plasminogen activator receptor. Gynecologic Oncology. Elsevier. https://doi.org/10.1016/j.ygyno.2005.09.038
chicago: Henic, Emir, Michael K Sixt, Stefan Hansson, Gunilla Høyer Hansen, and
Bertil Casslén. “EGF-Stimulated Migration in Ovarian Cancer Cells Is Associated
with Decreased Internalization, Increased Surface Expression, and Increased Shedding
of the Urokinase Plasminogen Activator Receptor.” Gynecologic Oncology.
Elsevier, 2006. https://doi.org/10.1016/j.ygyno.2005.09.038.
ieee: E. Henic, M. K. Sixt, S. Hansson, G. Høyer Hansen, and B. Casslén, “EGF-stimulated
migration in ovarian cancer cells is associated with decreased internalization,
increased surface expression, and increased shedding of the urokinase plasminogen
activator receptor,” Gynecologic Oncology, vol. 101, no. 1. Elsevier, pp.
28–39, 2006.
ista: Henic E, Sixt MK, Hansson S, Høyer Hansen G, Casslén B. 2006. EGF-stimulated
migration in ovarian cancer cells is associated with decreased internalization,
increased surface expression, and increased shedding of the urokinase plasminogen
activator receptor. Gynecologic Oncology. 101(1), 28–39.
mla: Henic, Emir, et al. “EGF-Stimulated Migration in Ovarian Cancer Cells Is Associated
with Decreased Internalization, Increased Surface Expression, and Increased Shedding
of the Urokinase Plasminogen Activator Receptor.” Gynecologic Oncology,
vol. 101, no. 1, Elsevier, 2006, pp. 28–39, doi:10.1016/j.ygyno.2005.09.038.
short: E. Henic, M.K. Sixt, S. Hansson, G. Høyer Hansen, B. Casslén, Gynecologic
Oncology 101 (2006) 28–39.
date_created: 2018-12-11T12:05:57Z
date_published: 2006-04-01T00:00:00Z
date_updated: 2026-08-26T13:04:22Z
day: '01'
doi: 10.1016/j.ygyno.2005.09.038
extern: '1'
fulldoi: https://doi.org/10.1016/j.ygyno.2005.09.038
intvolume: ' 101'
issue: '1'
language:
- iso: eng
month: '04'
oa_version: None
page: 28 - 39
publication: Gynecologic Oncology
publication_identifier:
issn:
- 0090-8258
publication_status: published
publisher: Elsevier
publist_id: '2194'
status: public
title: EGF-stimulated migration in ovarian cancer cells is associated with decreased
internalization, increased surface expression, and increased shedding of the urokinase
plasminogen activator receptor
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 101
year: '2006'
...