Differential Macromolecular Leakage from the Vasculature of Tumors

Tumor-induced neovascularization is essential for invasion, metastases, and exponential growth of solid tumors. The authors studied the differences in macromolecular leakage from the neovasculature of a fast-growing, early-metastasizing tumor, the Walker 256 carcinosarcoma, and a slow-growing, nonmetastasizing tumor, a rat chondrosarcoma. A 1-mm3 piece of the Walker 256 carcinoma or the chondrosarcoma was implanted in the cremaster muscle of rats. Five days after surgery the cremaster muscle with the implanted tumor was placed in a special bath containing Krebs solution such that the circulation and nerves from the animal to the cremaster were intact. Fluorescein isothiocyanate-labeled rat serum albumin (FITC-RSA) was injected (intra-arterially) into each rat to permit visualization of the vasculature by fluorescent microscopy. A closed-circuit television system was used to quantitate macromolecular leakage as a change in interstitial fluorescent intensity. Data are given as a relative fluorescent intensity (mean +/- standard error of the mean) in an area of the cremaster with tumor-induced neovascularization. These studies demonstrated that the vasculature induced by rapidly growing Walker 256 carcinosarcoma leak albumin freely when compared with the vasculature induced by the slow-growing chondrosarcoma. Furthermore, there was a significant increase in fluorescent intensity (albumin leakage) in the Walker tumor from 1 minute (24 +/- 3.0) to 30 minutes (49 +/- 5.6). In the normal cremaster area there was a significantly lower fluorescent intensity in the interstitium and a very slight increase with time (4 +/- 1.5 at 1 minute vs. 7 +/- 1.4 at 30 minutes). One interpretation of these data is that the mechanisms responsible for protein leakage from the vasculature of the Walker tumor may be involved in the fast growth and metastases of this tumor as compared with slower-growing tumors such as the chondrosarcoma.