Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1016/j.ejca.2003.11.033

Type

Journal article

Journal

Eur J Cancer

Publication Date

05/2004

Volume

40

Pages

1066 - 1072

Keywords

Autocrine Communication, Blotting, Western, Cell Division, Cell Line, Tumor, Humans, Interleukin-6, Male, Prostatic Neoplasms, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-2