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. 2002 Mar 15;109(6):777–785. doi: 10.1172/JCI14105

Figure 6.

Figure 6

Coordinated upregulation of Ang-2 and VEGFR-2 mediates tumor angiogenesis after intracranial implantation. (a–c) In situ hybridization of 1-week tumors demonstrates that Ang-2 and VEGFR-2 mRNA expression was induced in parallel in tumor and host endothelium (b and c), whereas only low VEGF mRNA levels were present within the tumor (a). (d–f) Sense controls for in situ hybridization. t, tumor mass; p, peritumoral cerebral tissue. (g–i) A strong Ang-2 and VEGFR-2 mRNA expression pattern persisted in 2-week tumors (h and i). VEGF mRNA expression, which was homogeneous at 1 week, became heterogeneous by 2 weeks after implantation (g). (j–m) Serial immunohistochemistry for PECAM (l) and VEGFR-2 (j, k, m) in 1-week (j and l) and 2-week tumors (m) confirms VEGFR-2 expression by endothelial cells of tumor and adjacent host vessels. Square in j indicates area of interest detailed in k. Arrows in k indicate VEGFR-2–positive vessels with perivascular cuff of invading tumor cells. (n and o) Serial immunohistochemistry for PECAM (n) and Ki-67 (o) reveals tumor endothelial cell proliferation. Asterisks indicate identical tumor vessels in serial sections. Arrows indicate Ki-67–positive endothelial cells. Bars represent 100 μm (a–i) and 50 μm (j–o).