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. 2015 Aug 28;5:192. doi: 10.3389/fonc.2015.00192

Figure 2.

Figure 2

Enzymatic HA depletion leads to normalization of tIP and normalization of tumor vasculature. (A) PEGPH20 rapidly normalizes tIP. Dose-dependent effect of PEGPH20 [0 (control), 0.015, 0.15, 1.5, 4.5, 10, and 15 mg/kg] on tumor tIP in HA-high PC3 prostate tumors over a 2-h period following intravenous administration (starting tIP ~40 mm Hg). Abbreviations: HA, hyaluronan; IFP, interstitial fluid pressure; min, minutes; PEGPH20, polyethylene glycol-conjugated (pegylated) human hyaluronidase PH20; tIP, tumor interstitial pressure. Adapted with permission from Thompson et al. (16) (B) PEGPH20 treatment leads to vascular expansion and formation of endothelial fenestrae. Representative fluorescent images of KPC tumor from vehicle-treated (top left panels) and PEGPH20-treated (bottom left panels) mice (n = 4 mice for each cohort). Scanning electron microscopy images of pancreatic blood vessels in KPC (upper two right panels) mice following treatment with either vehicle or PEGPH20 (n = 4 mice for each cohort) reveal endothelial fenestrations (white arrowheads) only in the tumor microvasculature. PEGPH20-treated KPC mice. Endothelia in the healthy pancreata of control PC mice are comparable to the untreated KPC tumor. Abbreviations: HA, hyaluronan; KPC, LSL-KrasG12D/+; LSLTrp53R172H/+; Pdx-1-Cre; PC, LSL-Trp53R172H/+; Pdx-1-Cre; PEGPH20, polyethylene glycol-conjugated (pegylated) recombinant human hyaluronidase PH20. Adapted with permission from Jacobetz et al. (40).