Bodey B, Bodey B, Siegel S E, Kaiser H E
Department of Pathology, School of Medicine, University of Southern California, Los Angeles, USA. Bodey
Anticancer Res. 1998 Jul-Aug;18(4A):2701-10.
The commencement of the complex process of carcinogenesis, and subsequent, rapid tumor growth and progression of mammalian neoplasms, including malignant melanomas, depends upon the continuous de novo formation of capillaries [i.e. neovascularization (NV)/neoplasm-related angiogenesis (NRA)]. The generation of a dedifferentiated, malignant, highly invasive cellular immunophenotype (CIP) and distant metastases, as aspects of constant neoplastic progression, are also NRA-dependent processes. Endothelial cells undergo rapid proliferation during malignant melanoma (MM) related angiogenesis. Human endoglin (CD105/EDG), is a homodimeric cell surface component of the transforming growth factor-beta (TGF-beta) type I receptor complex and is also a proliferation-associated antigen (PAA) expressed at high density on endothelial cells. Formalin fixed, paraffin-wax embedded, tissue sections (3-5 microns thick) of 25 MMs were employed for the assessment of EDG expression. An indirect, four-step, alkaline phosphatase (AP) (or diamino-benzidine [DAB]) conjugated, biotin-streptavidin based, antigen detection technique, employing the SN6h anti-EDG monoclonal antibody was conducted. Zymed's Histogold System was also utilized for immunocytological antigen detection. Strong expression (A; +3 to +4) of EDG on endothelial cells was demonstrated in all MM cases. The most striking feature of the newly formed neoplasm-related capillaries was the presence of an enlarged perivascular space. Blood vessels in several normal human tissues (cortex, cerebellum, thymus, tonsil, spleen, lymph node, skin) used as control tissues contained significantly lower levels of EDG (B and mostly C; +/- to +), in accordance with the extremely slow turnover rate of normal endothelial cells. Furthermore, a close apposition between the capillaries and the adjacent parenchyma was observed in these normal controls. MMs, like most mammalian neoplasms, are characterized by extensive neovascularization, and thus are candidates for anti-angiogenic therapy. Further studies should substantiate the importance of EDG expression in the earliest possible detection, diagnosis and NRA inhibition-based treatment of solid tumors, including MMs. The importance of TGF-beta in all of the various aspects of neoplastic transformation, as well as malignant disease progression should also be studied more extensively in the future.
包括恶性黑色素瘤在内的哺乳动物肿瘤发生复杂过程的起始，以及随后肿瘤的快速生长和进展，都依赖于毛细血管的持续重新形成[即新生血管形成（NV）/肿瘤相关血管生成（NRA）]。作为肿瘤持续进展的表现，去分化、恶性、高侵袭性细胞免疫表型（CIP）的产生和远处转移也是依赖NRA的过程。在内皮细胞在恶性黑色素瘤（MM）相关血管生成过程中经历快速增殖。人内皮糖蛋白（CD105/EDG）是转化生长因子-β（TGF-β）I型受体复合物的同型二聚体细胞表面成分，也是在内皮细胞上高密度表达的增殖相关抗原（PAA）。采用25例MM的福尔马林固定、石蜡包埋组织切片（3 - 5微米厚）评估EDG表达。采用间接的四步法碱性磷酸酶（AP）（或二氨基联苯胺[DAB]）偶联、基于生物素 - 链霉亲和素的抗原检测技术，使用SN6h抗EDG单克隆抗体进行检测。Zymed的Histogold系统也用于免疫细胞抗原检测。在所有MM病例中均显示内皮细胞上EDG呈强表达（A；+3至+4）。新形成的肿瘤相关毛细血管最显著的特征是存在扩大的血管周围间隙。用作对照组织的几种正常人体组织（皮质、小脑、胸腺、扁桃体、脾脏、淋巴结、皮肤）中的血管所含EDG水平显著较低（B且大多为C；+/-至+），这与正常内皮细胞极低的更新率一致。此外，在这些正常对照中观察到毛细血管与相邻实质紧密相邻。MM与大多数哺乳动物肿瘤一样，其特征是广泛的新生血管形成，因此是抗血管生成治疗的候选对象。进一步的研究应证实EDG表达在包括MM在内的实体瘤的尽早检测、诊断和基于NRA抑制的治疗中的重要性。未来也应更广泛地研究TGF-β在肿瘤转化以及恶性疾病进展的各个方面的重要性。
