Li Qing, Yu Ying, Bischoff Joyce, Mulliken John B, Olsen Bjorn R
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
J Pathol. 2003 Oct;201(2):296-302. doi: 10.1002/path.1443.
Haemangioma is the most common tumour of endothelial origin, occurring in 4-10% of Caucasian infants. It is characterized by rapid growth during the first year of postnatal life, followed by spontaneous regression from 1 to 7 years of age. The cell surface adhesion molecule CD146 has been identified as an endothelial cell marker. Despite advances in understanding the functional role of CD146 in normal endothelial cells and tumour progression, its expression and a possible role in an endothelial tumour have not been studied. As part of an investigation of endothelial cell alterations in infantile haemangioma, differential expression studies were performed with several known antigens and endothelial cell markers. Using immunohistochemical and flow cytometric analyses, cultured human dermal microvascular endothelial cells isolated from newborn foreskin (HDMEC) were compared with endothelial cells derived from haemangioma tissue (HemECs). In addition, immunohistochemistry was used to compare haemangioma tissues with normal human skin. Unexpectedly, cultured HemECs showed a significantly lower level of CD146 than HDMECs by both flow cytometric analysis and immunofluorescence staining. Using immunohistochemical studies, it was further demonstrated that endothelia in all haemangioma tissues, regardless of the tumour phase, showed negative immunoreactivity for CD146. In contrast, strong positive staining for CD146 was observed in the pericyte-like cells that surround the endothelial layers. These findings are believed to be relevant to the molecular basis of haemangioma. Furthermore, it is possible that antibodies against CD146 may be useful for separating haemangioma-derived endothelial cells from normal endothelial cells and pericytes.
血管瘤是最常见的内皮起源肿瘤,在4% - 10%的高加索婴儿中出现。其特征是在出生后第一年快速生长,随后在1至7岁时自发消退。细胞表面粘附分子CD146已被鉴定为内皮细胞标志物。尽管在理解CD146在正常内皮细胞和肿瘤进展中的功能作用方面取得了进展,但其在内皮肿瘤中的表达及可能作用尚未得到研究。作为对婴儿血管瘤内皮细胞改变研究的一部分,对几种已知抗原和内皮细胞标志物进行了差异表达研究。使用免疫组织化学和流式细胞术分析,将从新生儿包皮分离的培养人真皮微血管内皮细胞(HDMEC)与血管瘤组织来源的内皮细胞(HemECs)进行比较。此外,免疫组织化学用于将血管瘤组织与正常人类皮肤进行比较。出乎意料的是,通过流式细胞术分析和免疫荧光染色,培养的HemECs显示CD146水平明显低于HDMECs。使用免疫组织化学研究进一步证明,所有血管瘤组织中的内皮细胞,无论肿瘤阶段如何,对CD146均呈阴性免疫反应。相反,在内皮细胞层周围的类周细胞中观察到CD146的强阳性染色。这些发现被认为与血管瘤的分子基础相关。此外,抗CD146抗体可能有助于从正常内皮细胞和周细胞中分离出血管瘤来源的内皮细胞。