Vascular stroma formation in carcinoma in situ, invasive carcinoma, and metastatic carcinoma of the breast.
Vascular stroma formation in carcinoma in situ, invasive carcinoma, and metastatic carcinoma of the breast.
复制标题
DOI：
--
复制
发表时间：
1999-05
期刊：
影响因子：
--
通讯作者：
L. Brown;Anthony J. Guidi;S. Schnitt;L. Water;M. Iruela-Arispe;T. Yeo;K. Tognazzi;H. Dvorak
中科院分区：
文献类型：
--
作者：
L. Brown;Anthony J. Guidi;S. Schnitt;L. Water;M. Iruela-Arispe;T. Yeo;K. Tognazzi;H. Dvorak
血管基质的产生对于实体瘤的生长至关重要，涉及刺激和抑制因子以及调节细胞粘附、迁移和基因表达等功能的基质成分。为了更全面地了解乳腺癌中血管基质的形成，我们检测了血管生成因子血管通透因子（VPF）/血管内皮生长因子（VEGF）的表达； VPF/VEGF 受体 flt-1 和 KDR；血小板反应蛋白-1，据报道可抑制血管生成；对 68 名患者的 113 块乳腺组织冰冻切片进行 mRNA 原位杂交，检测基质成分 I 型胶原蛋白、总纤连蛋白、ED-A+ 纤连蛋白、多功能蛋白聚糖和核心蛋白聚糖，其中 28 块乳腺组织切片为非恶性肿瘤、18 块原位癌、56 块浸润性癌和 8 块转移性癌。在浸润性癌、原位癌和转移性癌中出现了非常相似的特征性表达谱，具有以下特征：VPF/VEGF的肿瘤细胞强表达；内皮细胞强烈表达 VPF/VEGF 受体；基质细胞和肿瘤细胞偶尔强烈表达血小板反应蛋白-1； I 型胶原、总纤连蛋白、ED-A+ 纤连蛋白、多功能蛋白聚糖和核心蛋白聚糖的基质细胞强表达。血管基质的形成先于侵袭，这增加了肿瘤细胞没有侵入正常乳腺基质而是侵入它们诱导的富含血管基质的可能性。同样，转移部位的肿瘤细胞似乎会诱导它们生长的血管基质。我们得出的结论是，一种独特的 mRNA 表达模式是乳腺癌中血管基质生成的特征，并且血管基质的形成不仅在原发肿瘤的生长中发挥作用，而且在侵袭和转移中发挥作用。
The generation of vascular stroma is essential for solid tumor growth and involves stimulatory and inhibiting factors as well as stromal components that regulate functions such as cellular adhesion, migration, and gene expression. In an effort to obtain a more integrated understanding of vascular stroma formation in breast carcinoma, we examined expression of the angiogenic factor vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF); the VPF/VEGF receptors flt-1 and KDR; thrombospondin-1, which has been reported to inhibit angiogenesis; and the stromal components collagen type I, total fibronectin, ED-A+ fibronectin, versican, and decorin by mRNA in situ hybridization on frozen sections of 113 blocks of breast tissue from 68 patients including 28 sections of breast tissue without malignancy, 18 with in situ carcinomas, 56 with invasive carcinomas, and 8 with metastatic carcinomas. A characteristic expression profile emerged that was remarkably similar in invasive carcinoma, carcinoma in situ, and metastatic carcinoma, with the following characteristics: strong tumor cell expression of VPF/VEGF; strong endothelial cell expression of VPF/VEGF receptors; strong expression of thrombospondin-1 by stromal cells and occasionally by tumor cells; and strong stromal cell expression of collagen type I, total fibronectin, ED-A+ fibronectin, versican, and decorin. The formation of vascular stroma preceded invasion, raising the possibility that tumor cells invade not into normal breast stroma but rather into a richly vascular stroma that they have induced. Similarly, tumor cells at sites of metastasis appear to induce the vascular stroma in which they grow. We conclude that a distinct pattern of mRNA expression characterizes the generation of vascular stroma in breast cancer and that the formation of vascular stroma may play a role not only in growth of the primary tumor but also in invasion and metastasis.