Blood Flow in Six Human Melanoma Xenograft Lines with Different Growth Characteristics

Abstract

Blood flow in six human melanoma xenograft lines grown s.c. in BALB/c-nu/nu mice was studied and analyzed in relation to tumor growth characteristics. Two different methods were used to measure blood flow, i.e., uptake of ⁸⁶Rb and clearance of ¹³³Xe. The percentage of the injected ⁸⁶Rb taken up per g of tumor tissue and the ¹³³Xe clearance rate were used as parameters for blood flow. The results achieved with these two methods were consistent.

Blood flow differed significantly among individual tumors of the same line, even for tumors of similar size. All lines showed a decrease in blood flow with increasing tumor volume. This was due to an increase in necrotic fraction as well as a decrease in blood supply per viable tumor cell. Blood flow also differed significantly among the xenograft lines. All lines showed a lower blood flow than the kidney, spleen, liver, and foot. The blood flow was generally lower in the xenograft lines than in the EMT6 and Lewis lung murine tumor lines. There was no correlation between tumor blood flow and volumetric growth rate.

The xenograft lines could be divided into two distinct groups of three lines each with respect to blood supply per viable tumor cell. The three lines showing a high blood supply also showed a high fraction of cells in S phase (23–31%), whereas the three lines showing a low blood supply had a low fraction of S-phase cells (11–13%). Thus, blood supply per viable tumor cell was probably decisive for the cell proliferation activity in the tumors. Moreover, necrotic fraction increased with increasing tumor volume, and the magnitude of this increase was largest for the three lines showing the lowest blood supply per viable tumor cell. These observations were possibly consequences of basic differences in vascular architecture between the two groups of xenograft lines.