MIGRATION AND PROLIFERATION OF ENDOTHELIAL CELLS IN PREFORMED AND NEWLY FORMED BLOOD-VESSELS DURING TUMOR ANGIOGENESIS
MIGRATION AND PROLIFERATION OF ENDOTHELIAL CELLS IN PREFORMED AND NEWLY FORMED BLOOD-VESSELS DURING TUMOR ANGIOGENESIS
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DOI：
10.1016/0026-2862(77)90141-8
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发表时间：
1977-01-01
影响因子：
3.1
通讯作者：
FOLKMAN, J
中科院分区：
文献类型：
--
作者：
AUSPRUNK, DH;FOLKMAN, J
研究了离角膜缘血管丛1mm处V2癌植入兔角膜后肿瘤诱导的毛细血管增殖。1-10天后，采用胸腺嘧啶放射自显影、电子显微镜、静脉注射胶体C和裂隙灯体视显微镜检查角膜缘血管。肿瘤植入1 d后，内皮细胞呈现表面突起，与再生内皮相似。第2天，细胞从预制血管向肿瘤植入物迁移。同时，细胞连接处松动，原有小静脉壁上出现新的腔隙。第4天组织学检测到毛细血管芽，第6天进入角膜基质。在热杀死肿瘤的对照眼中，没有发现新的血管。内皮细胞胸苷标记指数在第2天升高，在第3天达到8%的峰值。第4天后，标记细胞仅位于生长毛细血管的远端。标示指数为0.6-4%。在对照组中，3天后标记率低于0.7%。在肿瘤血管生成过程中，预先形成的内皮细胞向肿瘤刺激的主动迁移可能先于细胞增殖。这一序列是否发生在其他形式的新生血管中尚不清楚。一旦新的毛细血管出现，肿瘤诱导的血管通过类似于伤口诱导的毛细血管的机制延长。
Tumor-induced capillary proliferation was studied in the rabbit cornea after implantation of V2 carcinoma 1 mm from the limbal vascular plexus. Limbal vessels were examined 1-10 days later with: [3H]thymidine autoradiography, EM, i.v. injection of colloidal C, and slit-lamp stereomicroscopy. Endothelial cells displayed surface projections and resembled regenerating endothelium 1 day after tumor implant. At 2 days, cells emigrated from preformed vessels toward the tumor implant. Simultaneously, cell junctions loosened and new lumina appeared in the walls of existing venules. Capillary sprouts were detected histologically at day 4 and entered the corneal stroma by day 6. New vessels were never seen in control eyes implanted with heat-killed tumor. The thymidine labeling index of endothelium was elevated on day 2 and reached a peak of 8% on day 3. After day 4, labeled cells were located only near the distal tips of the growing capillaries. The labeling index ranged from 0.6-4%. In controls, labeling was less than 0.7% after 3 days. Active migration of preformed endothelial cells toward the tumor stimulus may precede cell proliferation during tumor angiogenesis. Whether this sequence occurs in other forms of neovascularization is unknown. Once new capillaries appear, tumor-induced vessels elongate by mechanisms similar to wound-induced capillaries.