Karelina T V, Eisen A Z
Division of Dermatology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cancer Detect Prev. 1998;22(5):438-44. doi: 10.1046/j.1525-1500.1998.00061.x.
Collagenase-1 (C1) is the predominant matrix metalloproteinase present in newly formed microvessels and serves as a marker of neovascularization. The expression of the oncofetal fragment of fibronectin (Fn-f) was found to be increased during angiogenesis. In the present study, we investigated the relationship between the expression of collagenase-1 and the oncofetal fragment of fibronectin in newly formed microvessels as markers of tumor angiogenesis. In aggressive skin tumors (i.e., morpheaform and recurrent basal cell carcinomas) and squamous cell carcinomas, neovascularization was associated with a marked increase in the number of C1-positive and Fn-f-positive microvessels. At the beginning of elongation, microvessels begin to produce C1 but lose their ability to express type IV collagen and FVIII-related antigen. Later, this endothelium produces both Fn-f and C1. As maturation of microvessels occurs, C1-containing endothelium fails to express Fn-f but begins to produce a type IV collagen-containing basement membrane and FVIII-related antigen. These studies show that there is a selective expression of both Fn-f and collagenase by immature endothelial cells. C1 production begins at early stages of blood vessel formation and continues throughout angiogenesis. In contrast, Fn-f expression is limited to later stages of vasculogenesis, indicating that these proteins are reliable markers of angiogenesis.
胶原酶-1（C1）是新形成的微血管中存在的主要基质金属蛋白酶，可作为新生血管形成的标志物。研究发现，在血管生成过程中，纤连蛋白的癌胚片段（Fn-f）表达增加。在本研究中，我们调查了作为肿瘤血管生成标志物的新形成微血管中胶原酶-1的表达与纤连蛋白癌胚片段之间的关系。在侵袭性皮肤肿瘤（即硬斑病样和复发性基底细胞癌）和鳞状细胞癌中，新生血管形成与C1阳性和Fn-f阳性微血管数量的显著增加相关。在伸长开始时，微血管开始产生C1，但失去表达IV型胶原和FVIII相关抗原的能力。后来，这种内皮细胞同时产生Fn-f和C1。随着微血管的成熟，含C1的内皮细胞不再表达Fn-f，但开始产生含IV型胶原的基底膜和FVIII相关抗原。这些研究表明，未成熟的内皮细胞会选择性表达Fn-f和胶原酶。C1在血管形成的早期阶段开始产生，并在整个血管生成过程中持续存在。相比之下，Fn-f的表达仅限于血管生成的后期阶段，这表明这些蛋白质是血管生成的可靠标志物。
