Figure 4

Sunitinib-induced hypoxia accelerates the generation of CSCs and VM in breast tumors of TA2 mice. A) Microcirculation patterns of tumors in mice treated with sunitinib. The number of EDVs decreased and more VM channels were present in mice during and after treatment compared with the animals administered placebo. Numerous EDVs rebounded when treatment was discontinued. The arrows indicate the VM channels formed by PAS-positive matrix and tumor cells. B) Quantification of VM channels in the treatment groups. VM channels increased during and after sunitinib treatment. C) Immunofluorescence analysis of endomucin and CD133 expression and Hydroxyprobe analysis of oxygen levels. More tumor cells were detected using the Hypoxypobe in the tumors of mice treated with sunitinib, and most were CD133⁺. D) Quantification of EDVs. E) Quantification of CD133⁺ cells in tumors. More CD133⁺ cells were present in the sunitinib-treated tumors. Scale bar = 100 μm, and the error bar indicates the SD.