Interstitial fluid pressure is increased in renal cell carcinoma xenografts

The purpose of this study was to test the hypothesis that renal cell carcin oma (RCC) exhibits an increased intratumoral interstitial fluid pressure (I T-IFP). Therefore, resected tumors from human primary (n = 23) or metastati c RCC (n = 3) were xenografted in SCID mice. The IFP of single tumor nodule s (n = 65) and normal mouse tissue (n = 195) was measured by means of the " wick-in-needle" technique. Data demonstrate that the mean IT-IFP at neoplas ia was 35 times greater than in normal tissue, and decreased precipitously at the tumor boundary. IT-IFP values tended to increase with the grade of m alignancy of the tumor cells and tumor size. The mean IT-IFP of xenografts derived from primary RCC was twice as high as that from metastatic RCC tiss ue. These findings indicate a biophysical barrier to drug delivery in RCC; this may, in concert with cellular-based drug resistance mechanisms, be an additional explanation for resistance of the tumor to certain blood-borne a nticancer therapies.