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绘制正常和恶性细胞来源的前列腺小体表面的促血管生成和抗血管生成因子。

Mapping pro- and antiangiogenic factors on the surface of prostasomes of normal and malignant cell origin.

机构信息

Rudbeck Laboratory C5, Department of Oncology, Uppsala, Sweden.

出版信息

Prostate. 2010 Jun 1;70(8):834-47. doi: 10.1002/pros.21117.

Abstract

BACKGROUND

Angiogenesis is the formation of new blood vessels by capillary sprouting from pre-existing vessels. Tumor growth is angiogenesis-dependent and the formation of new blood vessels is associated with the increased expression of angiogenic factors. Prostasomes are secretory granules produced, stored and released by the glandular epithelial cells of the prostate. We investigated the expression of selected angiogenic and anti-angiogenic factors on the surface of prostasomes of different origins as well as the direct effect of prostasomes on angiogenesis.

METHODS

VEGF, endothelin-1, endostatin, and thrombospondin-1 were determined on prostasomes from seminal fluid and human prostate cancer cell lines (DU145,PC-3,LNCaP) using different immunochemical techniques. Human dermal microvascular endothelial cells were incubated with seminal and DU145 cell-prostasomes and with radioactive thymidine. The effect of prostasomes on angiogenesis was judged by measuring the uptake of labeled thymidine. The presence of any deleterious effects of prostasomes on the endothelial cells was investigated using thymidine assay and confocal laser microscopy.

RESULTS

VEGF and endothelin-1 were determined on malignant cell-prostasomes (no difference between cell lines) but not determined on seminal prostasomes. The same applies for the expression of endostatin but with much higher expression on malignant cell-prostasomes with obvious differences between them. Seminal and DU145 cell-prostasomes were found to have anti-angiogenic effect which was more expressed by DU145 cell-prostasomes. No deleterious effect of prostasomes on endothelial function was detected using either thymidine assay or microscopy.

CONCLUSIONS

Prostasomes contain pro- and anti-angiogenic factors that function to counteract each other unless the impact from one side exceeds the other to bring about dysequilibrium.

摘要

背景

血管生成是指毛细血管从预先存在的血管中发芽形成新的血管。肿瘤的生长依赖于血管生成,新血管的形成与血管生成因子表达的增加有关。前列腺小体是由前列腺腺上皮细胞产生、储存和释放的分泌颗粒。我们研究了不同来源的前列腺小体表面上选定的血管生成和抗血管生成因子的表达,以及前列腺小体对血管生成的直接作用。

方法

使用不同的免疫化学技术,在来自精液和人前列腺癌细胞系(DU145、PC-3、LNCaP)的前列腺小体上测定 VEGF、内皮素-1、内皮抑素和血栓素-1。用人真皮微血管内皮细胞孵育精液和 DU145 细胞-前列腺小体以及放射性胸腺嘧啶。通过测量标记胸腺嘧啶的摄取来判断前列腺小体对血管生成的影响。通过胸腺嘧啶测定和共聚焦激光显微镜检查来研究前列腺小体对内皮细胞是否存在任何有害影响。

结果

在恶性细胞前列腺小体(细胞系之间无差异)上测定了 VEGF 和内皮素-1,但在精液前列腺小体上未测定到。内皮抑素的表达也是如此,但在恶性细胞前列腺小体上表达更高,且差异明显。发现精液和 DU145 细胞前列腺小体具有抗血管生成作用,DU145 细胞前列腺小体的表达更为明显。无论是使用胸腺嘧啶测定还是显微镜检查,都没有发现前列腺小体对内皮功能有任何有害影响。

结论

前列腺小体包含促血管生成和抗血管生成因子,它们相互作用以达到平衡,除非一方的影响超过另一方,导致失衡。

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