Abnormalities in pericytes on blood vessels and endothelial sprouts in tumors
Abnormalities in pericytes on blood vessels and endothelial sprouts in tumors
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DOI：
10.1016/s0002-9440(10)64920-6
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发表时间：
2002-03-01
影响因子：
6
通讯作者：
McDonald, DM
中科院分区：
文献类型：
--
作者：
Morikawa, S;Baluk, P;McDonald, DM
肿瘤血管的内皮细胞有充分的证据表明发生了改变，但不太清楚这些血管上的周细胞是否异常甚至缺失。在此，我们报道了在小鼠三种不同的自发性或移植性肿瘤的100 μ m厚切片中，通过共聚焦显微镜观察，α-平滑肌肌动蛋白（α-SMA）和结蛋白免疫反应性周细胞存在于>97%的血管上。然而，细胞有多种异常。不像周细胞;在正常胰岛的毛细血管上，有结蛋白但没有α-SMA免疫反应性，在RIP-Tag 2转基因小鼠的胰岛素瘤中毛细血管大小的血管上的周细胞表达结蛋白和α-SMA。此外，RIP-Tag 2肿瘤中的周细胞，以及MCa-IV乳腺癌和刘易斯肺癌中的周细胞，与内皮细胞有异常松散的联系，并将细胞质突起延伸到肿瘤组织深处。在RIP-Tag 2肿瘤中，α-SMA阳性周细胞也覆盖了73%的内皮芽，在其他肿瘤中，覆盖了92%的芽。事实上，在所有三种类型的肿瘤中，周细胞袖明显长于CD 31免疫反应性内皮细胞芽本身。所有三种肿瘤还含有类似于周细胞但与血管无关的α-SMA阳性肌成纤维细胞。我们的结论是，周细胞存在于大多数肿瘤血管，但有多种异常，包括标志物蛋白的表达改变。与以前的一些研究相反，在本研究中发现的肿瘤血管上几乎无处不在的周细胞的存在可能归因于我们使用结蛋白和α-SMA作为标记物和100 μ m厚的组织切片。周细胞与内皮芽的关联提高了参与肿瘤芽生长或收缩的可能性。
Endothelial cells of tumor vessels have well-documented alterations, but it is less clear whether pericytes on these vessels are abnormal or even absent. Here we report that alpha-smooth muscle actin (alpha-SMA) and desmin-immunoreactive pericytes; were present on >97% of blood vessels viewed by confocal microscopy in 100-mum-thick sections of three different spontaneous or implanted tumors In mice. However, the cells had multiple abnormalities. Unlike pericytes; on capillaries in normal pancreatic islets, which had desmin but not alpha-SMA immunoreactivity, pericytes on capillary-size vessels in insulinomas in RIP-Tag2 transgenic mice expressed both desmin and alpha-SMA. Furthermore, pericytes in RIP-Tag2 tumors, as well as those in MCa-IV breast carcinomas and Lewis lung carcinomas, had an abnormally loose association with endothelial cells and extended cytoplasmic processes deep into the tumor tissue. alpha-SMA-positive pericytes also covered 73% of endothelial sprouts in RIP-Tag2 tumors and 92% of sprouts in the other tumors. Indeed, pericyte sleeves were significantly longer than the CD31-immunoreactive endothelial cell sprouts themselves in all three types of tumors. All three tumors also contained alpha-SMA-positive myo-fibroblasts that resembled pericytes but were not associated with blood vessels. We conclude that pericytes are present on most tumor vessels but have multiple abnormalities, including altered expression of marker proteins. In contrast to some previous studies, the almost ubiquitous presence of pericytes on tumor vessels found in the present study may be attributed to our use of both desmin and alpha-SMA as markers and 100-mum-thick tissue sections. The association of pericytes with endothelial sprouts raises the possibility of an involvement in sprout growth or retraction in tumors.