Schlingemann R O, Rietveld F J, Kwaspen F, van de Kerkhof P C, de Waal R M, Ruiter D J
Department of Pathology, Nijmegen University Cancer Center, The Netherlands.
Am J Pathol. 1991 Jun;138(6):1335-47.
The structure and function of the tumor microvasculature is of great interest for cancer biology, diagnosis, and therapy. The distribution of endothelial cells, pericytes, and basal lamina in tumors is not well documented. In this study, the authors investigated the distribution of markers for these different components in a series of malignant human tumors and in human granulation tissue, both situations with extensive angiogenesis. Their results show a striking heterogeneity in the expression of markers for pericytes and endothelial cells between different tumors, but also within a single tumor lesion. To be able to distinguish between these two adjacent cell types decisively, all marker studies were carried out both on the light and the electron microscopical level and compared with staining results in granulation tissue of cutaneous wounds in healthy volunteers and of decubitus lesions. In granulation tissue of decubitus lesions, well-defined zones with increasing levels of maturation can be delineated. It was found that antibodies recognizing von Willebrand factor often failed to stain the tumor capillaries. Of the pericyte markers, alpha-smooth muscle actin was only locally expressed by pericytes in the tumor vasculature, whereas the high-molecular-weight melanoma-associated antigen, a chondroitin sulfate proteoglycan, stained the microvasculature broadly. Staining of the basal lamina components collagen type IV and laminin was, within the tumor, not restricted to the microvasculature. From their findings the authors conclude that 1) for the visualization of the tumor vasculature, antibodies recognizing endothelial markers, especially monoclonal antibodies PAL-E and BMA 120, are preferable to those recognizing pericytes or basal lamina; 2) within the microvasculature of tumors and granulation tissue, a heterogeneity of expression of endothelial and pericyte markers is observed; 3) during the formation of granulation tissue, all three microvascular components can be demonstrated already in the histologically earliest stage, suggesting not only an involvement of endothelial cells but also of pericytes and basal lamina in the initial steps of angiogenesis in wound healing.
肿瘤微血管的结构与功能在癌症生物学、诊断及治疗方面备受关注。肿瘤中内皮细胞、周细胞及基膜的分布情况尚无充分记载。在本研究中，作者调查了一系列人类恶性肿瘤及人类肉芽组织（二者均存在广泛血管生成）中这些不同成分标志物的分布。他们的结果显示，不同肿瘤之间以及同一肿瘤病灶内，周细胞和内皮细胞标志物的表达存在显著异质性。为了能够明确区分这两种相邻细胞类型，所有标志物研究均在光学和电子显微镜水平上进行，并与健康志愿者皮肤伤口肉芽组织及褥疮病变的染色结果进行比较。在褥疮病变的肉芽组织中，可以勾勒出成熟度逐渐增加的明确区域。研究发现，识别血管性血友病因子的抗体常常无法使肿瘤毛细血管染色。在周细胞标志物中，α-平滑肌肌动蛋白仅在肿瘤脉管系统的周细胞中局部表达，而高分子量黑素瘤相关抗原（一种硫酸软骨素蛋白聚糖）则广泛地使微血管染色。肿瘤内基膜成分IV型胶原和层粘连蛋白的染色并不局限于微血管。基于这些发现，作者得出以下结论：1）对于肿瘤脉管系统的可视化，识别内皮标志物的抗体，尤其是单克隆抗体PAL-E和BMA 120，优于识别周细胞或基膜的抗体；2）在肿瘤和肉芽组织的微血管系统中，观察到内皮细胞和周细胞标志物表达的异质性；3）在肉芽组织形成过程中，在组织学最早阶段即可显示所有三种微血管成分，这表明在伤口愈合的血管生成初始步骤中，不仅内皮细胞参与其中，周细胞和基膜也参与其中。
