肝素的定位和精细结构调节伯基特淋巴瘤的生长。

Heparin localization and fine structure regulate Burkitt's lymphoma growth.

作者信息

Berry David, Lynn David M, Berry Eric, Sasisekharan Ram, Langer Robert

机构信息

Harvard Medical School, Boston, MA 02215, USA.

出版信息

Biochem Biophys Res Commun. 2006 Sep 29;348(3):850-6. doi: 10.1016/j.bbrc.2006.07.128. Epub 2006 Jul 31.

DOI:10.1016/j.bbrc.2006.07.128

PMID:16904641

Abstract

Burkitt's lymphoma (BL) is a B-cell malignancy associated with the Epstein-Barr virus (EBV). Mounting evidence has implicated heparan sulfate proteoglycans and heparan sulfate-like glycosaminoglycans (HSGAGs) in the initiation, severity, and progression of the malignancy. The importance of HSGAGs in regulating BL cell growth was therefore examined. Extracellular exogenous heparin inhibited cell growth >30%, while heparin internalized with poly(beta-amino ester)s promoted proliferation up to 58%. The growth-modulating effects of heparin and internalized heparin were dependent on cell surface HSGAGs, PI3K, and Erk/Mek. Treatment of cells with protamine sulfate or with heparinases potently inhibited proliferation, with the greatest effects induced by heparinase I. Cell surface HSGAGs therefore play an important role in regulating BL proliferation and may offer a potential target for therapeutic intervention.

摘要

伯基特淋巴瘤（BL）是一种与爱泼斯坦-巴尔病毒（EBV）相关的B细胞恶性肿瘤。越来越多的证据表明，硫酸乙酰肝素蛋白聚糖和硫酸乙酰肝素样糖胺聚糖（HSGAGs）与这种恶性肿瘤的发生、严重程度及进展有关。因此，研究了HSGAGs在调节BL细胞生长中的重要性。细胞外源性肝素抑制细胞生长超过30%，而与聚（β-氨基酯）内化的肝素促进增殖高达58%。肝素和内化肝素的生长调节作用取决于细胞表面的HSGAGs、PI3K和Erk/Mek。用硫酸鱼精蛋白或肝素酶处理细胞可有效抑制增殖，其中肝素酶I诱导的效果最为显著。因此，细胞表面的HSGAGs在调节BL增殖中起重要作用，可能为治疗干预提供潜在靶点。