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Insulin-like growth factor-I receptor activity is essential for Kaposi's sarcoma growth and survival.

Abstract：

:Kaposi's sarcoma (KS) is a highly vascular tumour and is the most common neoplasm associated with human immunodeficiency virus (HIV-1) infection. Growth factors, in particular vascular endothelial growth factor (VEGF), have been shown to play an important role in its development. The role of insulin-like growth factors (IGFs) in the pathophysiology of different tumours led us to evaluate the role of IGF system in KS. The IGF-I receptors (IGF-IR) were identified by immunohistochemistry in biopsies taken from patients with different AIDS/HIV-related KS stages and on KSIMM cells (an established KS-derived cell line). Insulin-like growth factor-I is a growth factor for KSIMM cells with a maximum increase of 3H-thymidine incorporation of 130 +/- 27.6% (P < 0.05) similar to that induced by VEGF and with which it is additive (281 +/- 13%) (P < 0.05). Moreover, specific blockade of the receptor (either by alpha IR3 antibody or by picropodophyllin, a recently described selective IGF-IR tyrosine phosphorylation inhibitor) induced KSIMM apoptosis, suggesting that IGF-IR agonists (IGF-I and -II) mediate antiapoptotic signals for these cells. We were able to identify an autocrine loop essential for KSIMM cell survival in which IGF-II is the IGF-IR agonist secreted by the cells. In conclusion, IGF-I pathway inhibition is a promising therapeutical approach for KS tumours.

journal_name

Br J Cancer

journal_title

British journal of cancer

authors

Catrina SB,Lewitt M,Massambu C,Dricu A,Grünler J,Axelson M,Biberfeld P,Brismar K

doi

10.1038/sj.bjc.6602408

subject

Has Abstract

pub_date

2005-04-25 00:00:00

pages

1467-74

issue

8

eissn

0007-0920

issn

1532-1827

pii

6602408

journal_volume

92

pub_type

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