Insulin-like growth factor-I receptor activity is essential for Kaposi's sarcoma growth and survival.
Insulin-like growth factor-I receptor activity is essential for Kaposi's sarcoma growth and survival.
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胰岛素样生长因子I受体活性对于卡波西肉瘤的生长和生存至关重要。
DOI：
10.1038/sj.bjc.6602408
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发表时间：
2005-04-25
影响因子：
8.8
通讯作者：
Brismar, K
中科院分区：
文献类型：
--
作者：
Catrina, SB;Lewitt, M;Massambu, C;Dricu, A;Grünler, J;Axelson, M;Biberfeld, P;Brismar, K
卡波西氏肉瘤（KS）是一种高度血管化的肿瘤，是与人类免疫缺陷病毒（HIV-1）感染相关的最常见肿瘤。生长因子，特别是血管内皮生长因子（VEGF），已被证明在其发展中发挥重要作用。胰岛素样生长因子（IGFs）在不同肿瘤的病理生理学中的作用使我们评估IGF系统在KS中的作用。IGF-I受体（IGF-IR）通过免疫组织化学在取自不同AIDS/HIV相关KS分期患者的活检组织和KSIMM细胞（一种已建立的KS衍生细胞系）中进行鉴定。胰岛素样生长因子-I是KSIMM细胞的生长因子，其最大3 H-TdR掺入增加量为130±27.6%（P<0.05），与VEGF相似，两者相加（281±13%）（P<0.05）。此外，受体的特异性阻断（通过α IR 3抗体或苦鬼臼脂素，一种最近描述的选择性IGF-IR酪氨酸磷酸化抑制剂）诱导KSIMM凋亡，表明IGF-IR激动剂（IGF-I和IGF-II）介导这些细胞的抗凋亡信号。我们能够确定KSIMM细胞存活所必需的自分泌环，其中IGF-II是细胞分泌的IGF-IR激动剂。总之，IGF-I通路抑制是KS肿瘤的一种有前途的治疗方法。
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 α 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.
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影响因子：
27.4
作者：
Catrina, AI;Ulfgren, AK;Klareskog, L
通讯作者：
Klareskog, L
DOI：
10.1073/pnas.83.3.664
发表时间：
1986-02-01
影响因子：
11.1
作者：
FLIER, JS;USHER, P;MOSES, AC
通讯作者：
MOSES, AC
DOI：
10.1073/pnas.94.3.979
发表时间：
1997-02-04
影响因子：
11.1
作者：
Masood, R;Cai, J;Gill, PS
通讯作者：
Gill, PS
影响因子：
3.8
作者：
Albini, A;Paglieri, I;Benelli, R
通讯作者：
Benelli, R
影响因子：
4.8
作者：
Albini, A;Florio, T;Schettini, G
通讯作者：
Schettini, G