Functional mitochondria detected by 18F-FBnTP is a prominent trait of tumor cell proliferation in vivo

Objectives Mitochondrial dysfunction, rapid cell proliferation, enhanced glycolysis and a hypoxic microenvironment are claimed to be characteristics of tumor aggressiveness and resistance to chemotherapy. However, the role of mitochondria in cell proliferation at the tumor level is far from clear. Mitochondrial membrane potential (Δψm) is a comprehensive correlate of the organelle’s bioenergetic function. We analyzed the relationship among these biological properties and the Δψm probe 18F-FBnTP (fluorobenzyltriphenyl phosphonium) in rat mammary tumors.

Methods Studies were carried out in mammary tumor-bearing Lewis rats (n = 5). 18F-FBnTP, 14C-thymidine (THD), and the hypoxic agent pimonidazole (PMIO) were administered IV. Three samples were collected from each tumor and tissue sections were prepared. FBnTP and THD autoradiography as well as histoimmunostaining of PIMO and the glucose transporter GLUT 1 were carried out. The spatial relationships and quantitative relationships were analyzed.

Results A strong spatial co-localization of FBnTP and THD was observed in all tumor sections. Quantitatively, a direct linear correlation between FBnTP and THD was measured with mean R2 = 0.73±0.15, slope = 0.79±0.18 and intercept = 0.19±0.167. Regions of high FBnTP and THD binding were characterized by low PIMO and GLUT 1 expression. A significant inverse relationship between FBnTP and THD vs. PIMO and GLUT1 was found.

Conclusions This study provides a clear insight at the tumor level into the role of mitochondria in cancer cell proliferation. The strong spatial and quantitative relationships suggest that in the rat mammary tumors, mitochondrial oxidative metabolism and aerobic conditions are prerequisites of cancer cell proliferation. These data cast doubt on the common notion that mitochondrial dysfunction and consecutive anaerobic glycolysis are widely present in cancers