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.