Wang Gui-Min, Kovalenko Bruce, Wilson E Lynette, Moscatelli David
Department of Cell Biology and the Kaplan Cancer Center, New York University School of Medicine, New York, NY 10016, USA.
Prostate. 2007 Jun 15;67(9):968-75. doi: 10.1002/pros.20582.
The proximal region of the prostatic ducts harbor the prostatic epithelial stem cells. As stem cell niches in other organs are highly vascularized, we determined if the proximal region is more highly vascularized than the remaining regions of the prostate. The effect of androgen on vascular density in the different prostatic regions was also examined.
Sections from prostates were immunostained with antibodies to CD31, and the vascular density in proximal, intermediate, and distal regions was calculated by image analysis software. Vascular density was compared in prostates from castrated mice that received daily inoculations of testosterone or vehicle alone for 3 days. To examine the role of angiogenic factors in the response to androgen, some animals were also treated with soluble VEGF receptor-2-Fc or Tie-2--Fc fusion proteins, which inhibit the activities of VEGF and angiopoietins, respectively. The endothelial proliferative response to androgen was determined by double staining sections with antibodies to CD31 and Ki-67.
In prostates from intact mice, vascular density was highest in the proximal region and lowest in the distal region. Administration of testosterone to castrated mice increased vascular density to the greatest extent in the distal and intermediate regions. The increase in vascular density required VEGF and the angiopoietins. Endothelial cell proliferation was less sensitive to androgen in the proximal region than the remainder of the prostate.
Vascular density is highest in the proximal region of the prostate, but the proximal vessels are less responsive to testosterone.
前列腺导管的近端区域含有前列腺上皮干细胞。由于其他器官中的干细胞微环境具有高度血管化,我们确定前列腺的近端区域是否比前列腺的其余区域血管化程度更高。还研究了雄激素对不同前列腺区域血管密度的影响。
用抗CD31抗体对前列腺切片进行免疫染色,通过图像分析软件计算近端、中间和远端区域的血管密度。比较了接受每日睾酮注射或单独注射赋形剂3天的去势小鼠前列腺中的血管密度。为了研究血管生成因子在对雄激素反应中的作用,一些动物还用可溶性VEGF受体-2-Fc或Tie-2-Fc融合蛋白进行了处理,它们分别抑制VEGF和血管生成素的活性。通过用抗CD31和Ki-67抗体对切片进行双重染色来确定内皮细胞对雄激素的增殖反应。
在完整小鼠的前列腺中,近端区域的血管密度最高,远端区域最低。给去势小鼠注射睾酮后,远端和中间区域的血管密度增加幅度最大。血管密度的增加需要VEGF和血管生成素。近端区域的内皮细胞增殖对雄激素的敏感性低于前列腺的其余部分。
前列腺近端区域的血管密度最高,但近端血管对睾酮的反应较小。