Figure 12.

Activated HIF1a downregulates Cav-1 in the tumor stromal compartment: Stromal co-localization with PKM2 and LDHB. (A) Cav-1 immunostaining. To assess whether expression of activated HIF1a in fibroblasts results in mammary tumors with a Cav-1 negative fibroblastic stromal compartment, consecutive frozen sections were cut from mammary tumors that were grown with fibroblasts expressing activated HIF1a. Note that Cav-1 expression is substantially reduced in the stromal compartment of these tumors, but is selectively retained in the micro-vasculature (endothelial cells), exactly as is observed in human breast cancers in vivo. Tumor cells are marked by GFP (green fluorescence). (B) PKM2 and LDHB immunostaining. The presence of these Cav-1 negative fibroblasts was confirmed in consecutive sections (compare with part A, shown at right) by employing antibodies directed against glycolytic enzymes, such as PKM2 and LDHB. Note that PKM2 and LDHB immuno-staining nicely coincides with the Cav-1 negative stromal area in these MDA-MB-231 tumor tissue sections, and does not significantly overlap with the tumor cells which are marked by GFP (green fluorescence).