BLOOD-FLOW, OXYGEN-CONSUMPTION, AND TISSUE OXYGENATION OF HUMAN-BREAST CANCER XENOGRAFTS IN NUDE RATS

Abstract

Human breast cancer xenografts in T-cell-deficient rnu/rnu rats permit the detailed and systematic study of blood flow, oxygen supply, and characterization of the cellular microenvironment of human tumors in vivo. Using an epigastric pouching technique, it is possible to obtain a tissue-isolated preparation which makes direct studies of blood flow and oxygen supply in human tumors feasible. So far, medullary and squamous cell carcinomas of the breast from different patients have been investigated under well-defined systemic conditions. At comparable tumor sizes, the average blood flow rate through human breast-cancer xenografts is higher in medullary than in squamous cell carcinomas (0.17 versus 0.10 ml .cntdot. g-1 min-1). Blood flow per unit tumor mass significantly decreases with increasing wet weight. No significant differences are obvious when comparing the flow values of pre- and postmenopausal tumors or of cancer tissues with different hormone receptor capacities. On the average, the oxygen consumption rates of human breast cancer xenografts are 10.4 in medullary and 7.7 .mu.l O2 .cntdot. g-1 in squamous cell carcinomas. With increasing tumor mass, the O2 consumption rate per unit weight significantly decreases. This decrease parallels the respective decline of tumor blood flow, implying that the O2 consumption rate of the cancer cells in vivo is mostly limited by the nutritive blood flow, i.e., by the O2 availability to the tumors. Due to a restricted blood supply, the O2 utilization of human breast cancer xenografts is high. Tissue oxygenation in microareas of human breast cancers xenotransplanted s.c. into nude rats is mostly inadequate. As a consequence, tissue hypoxia and anoxia are common findings even in very early growth stages. Due to marked intra- and intertumor variabilities in blood flow, heterogeneities in the tissue oxygenation are characteristic features of human breast cancer xenografts. From the results obtained it is concluded that human breast cancers growing as xenografts in rnu/rnu rats may be useful tools for cancer research, especially for investigations of blood flow, tissue oxygenation, and substrate turnover.