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An autocrine loop for vascular endothelial growth factor is established in prostate cancer cells generated after prolonged treatment with interleukin 6

Steiner, H ; Berger, AP ; Godoy-Tundidor, S ; Bjartell, Anders LU ; Lilja, Hans LU orcid ; Bartsch, G ; Hobisch, A and Culig, Z (2004) In European Journal of Cancer 40(7). p.1066-1072
Abstract
Concentrations of interleukin 6 (IL-6) and its receptor are increased in human prostate cancer. Prostate cancer LNCaP-IL-6+ cells, established after prolonged treatment with IL-6, have been found to acquire a growth advantage. Vascular endothelial growth factor (VEGF) may accelerate the growth of various tumours by stimulation of VEGF receptor 2 (VEGFR-2). To understand better the regulation of proliferation of LNCaP-IL-6+ cells, the expression of VEGF and VEGFR-2 was here investigated in the LNCaP-IL-6+ subline. VEGF was measured in cellular supernatants by enzyme-linked immunoassay. The expression of VEGFR-2 was assessed by Western blot. LNCaP-IL-6+ and control LNCaP-IL-6- cells were treated with a neutralising antibody against VEGFR-2.... (More)
Concentrations of interleukin 6 (IL-6) and its receptor are increased in human prostate cancer. Prostate cancer LNCaP-IL-6+ cells, established after prolonged treatment with IL-6, have been found to acquire a growth advantage. Vascular endothelial growth factor (VEGF) may accelerate the growth of various tumours by stimulation of VEGF receptor 2 (VEGFR-2). To understand better the regulation of proliferation of LNCaP-IL-6+ cells, the expression of VEGF and VEGFR-2 was here investigated in the LNCaP-IL-6+ subline. VEGF was measured in cellular supernatants by enzyme-linked immunoassay. The expression of VEGFR-2 was assessed by Western blot. LNCaP-IL-6+ and control LNCaP-IL-6- cells were treated with a neutralising antibody against VEGFR-2. VEGF concentrations were 20-fold higher in LNCaP-IL-6+ than in LNCaP-IL-6- cells. The stimulatory effect of IL-6 on VEGF production was abolished by an inhibitor of the signalling pathway for phosphoinositol 3 kinase in LNCaP-IL-6+ and LNCaP-IL-6- cells. Exogenous VEGF did not stimulate proliferation in either LNCaP-IL-6+ cells or controls. VEGFR-2 was detected only in LNCaP-IL-6+ cells, in which the neutralising antibody caused a partial inhibition of cell proliferation. It was concluded that a VEGF autocrine loop is established in prostate cancer cells generated after chronic treatment with IL-6. Because of the upregulation of IL-6 in patients with prostate cancer, these findings might be clinically relevant. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
factor, autocrine signalling, vascular endothelial growth, interleukin 6, prostate cancer, cytokines
in
European Journal of Cancer
volume
40
issue
7
pages
1066 - 1072
publisher
Elsevier
external identifiers
  • wos:000221467400028
  • pmid:15093584
  • scopus:1942517751
  • pmid:15093584
ISSN
1879-0852
DOI
10.1016/j.ejca.2003.11.033
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Department of Translational Medicine (013017500), Urology (013243400), Clinical Chemistry, Malmö (013016000), Division of Urological Cancers (013243420)
id
4431d3f9-7c0a-4e85-b668-a731c7b127fd (old id 279074)
date added to LUP
2016-04-01 11:49:39
date last changed
2022-01-26 18:52:22
@article{4431d3f9-7c0a-4e85-b668-a731c7b127fd,
  abstract     = {{Concentrations of interleukin 6 (IL-6) and its receptor are increased in human prostate cancer. Prostate cancer LNCaP-IL-6+ cells, established after prolonged treatment with IL-6, have been found to acquire a growth advantage. Vascular endothelial growth factor (VEGF) may accelerate the growth of various tumours by stimulation of VEGF receptor 2 (VEGFR-2). To understand better the regulation of proliferation of LNCaP-IL-6+ cells, the expression of VEGF and VEGFR-2 was here investigated in the LNCaP-IL-6+ subline. VEGF was measured in cellular supernatants by enzyme-linked immunoassay. The expression of VEGFR-2 was assessed by Western blot. LNCaP-IL-6+ and control LNCaP-IL-6- cells were treated with a neutralising antibody against VEGFR-2. VEGF concentrations were 20-fold higher in LNCaP-IL-6+ than in LNCaP-IL-6- cells. The stimulatory effect of IL-6 on VEGF production was abolished by an inhibitor of the signalling pathway for phosphoinositol 3 kinase in LNCaP-IL-6+ and LNCaP-IL-6- cells. Exogenous VEGF did not stimulate proliferation in either LNCaP-IL-6+ cells or controls. VEGFR-2 was detected only in LNCaP-IL-6+ cells, in which the neutralising antibody caused a partial inhibition of cell proliferation. It was concluded that a VEGF autocrine loop is established in prostate cancer cells generated after chronic treatment with IL-6. Because of the upregulation of IL-6 in patients with prostate cancer, these findings might be clinically relevant.}},
  author       = {{Steiner, H and Berger, AP and Godoy-Tundidor, S and Bjartell, Anders and Lilja, Hans and Bartsch, G and Hobisch, A and Culig, Z}},
  issn         = {{1879-0852}},
  keywords     = {{factor; autocrine signalling; vascular endothelial growth; interleukin 6; prostate cancer; cytokines}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{1066--1072}},
  publisher    = {{Elsevier}},
  series       = {{European Journal of Cancer}},
  title        = {{An autocrine loop for vascular endothelial growth factor is established in prostate cancer cells generated after prolonged treatment with interleukin 6}},
  url          = {{http://dx.doi.org/10.1016/j.ejca.2003.11.033}},
  doi          = {{10.1016/j.ejca.2003.11.033}},
  volume       = {{40}},
  year         = {{2004}},
}