Hyaluronidase reduces the interstitial fluid pressure in solid tumours in a non-linear concentration-dependent manner

Hyaluronidase has gained increasing interest as an adjuvant in local and systemic cancer therapy, despite the incomplete knowledge of its physiological function. To this end, direct intratumoral injection of bovine testicular hyaluronidase (500, 1600 or 7500 U in 50 microl phosphate-buffered saline (PBS)) was performed in orthotopic (o.t.) osteosarcoma xenografts grown in the hind leg of nude mice. Control tumours received 50 microl PBS alone or supplemented with 10% bovine serum albumin (BSA). Central tumour interstitial fluid pressure (IFP) and mean arterial blood pressure (MABP) were measured using the wick-in-needle technique and after cannulation of the carotid artery, respectively. IFP was 32 +/- 8 mmHg (n = 44, mean +/- SD) in untreated tumours and there was a significant correlation between tumour IFP and volume (P < 0.01). The hyaluronidase injection reduced IFP to 63-84% after 1 h compared with controls (P < 0.05) and in a non-linear concentration-dependent manner. MABP was not affected significantly. In conclusion, an intratumoral hyaluronidase injection might reduce IFP temporally in solid osteosarcoma xenografts.