Tumour growth results in changes in placental amino acid transport in the rat: a tumour necrosis factor α-mediated effect Available to Purchase

The implantation of a fast growing tumour (Yoshida AH-130 ascites hepatoma) to late pregnant rats resulted in no changes in fetal growth, this possibly being associated with an important increase in the fetal uptake of maternal-derived amino acids [Carbó, López-Soriano and Argilés (1995) Endocrinology 136, 3579-3584]. The present investigation was undertaken to see whether the presence of the tumour induced changes in placental transport systems. For alanine transport, although no changes in affinity (K_m) were observed, tumour growth resulted in a 192% increase in V_max. in the Na⁺-independent component. Kinetic analysis of the Na⁺-dependent component resulted in two clearly different components: while the low-affinity and high-capacity component was unaffected by tumour growth, the high-affinity, low-capacity component of the tumour-bearing rats showed an important increase in V_max. (78%). With regard to leucine transport, tumour burden induced important increases in the Na⁺-independent component, not only in K_m (262%) but also in V_max. (189%). Since elevated tumour necrosis factor-α (TNF) concentrations have been reported in this kind of tumour model, we performed the same type of transport experiments in rats chronically treated with TNF, the results obtained showing great similarities with those observed with tumour growth. The V_max. of Na⁺-independent alanine transport was also increased by the cytokine (104%) while no changes were observed in affinity. TNF treatment also induced an increase in the V_max. (67%) of the Na⁺-dependent (high-affinity, low-capacity) component while no changes in affinity were observed. Concerning leucine kinetics, TNF treatment, as in the case of tumour growth, also increased K_m (155%) and V_max. (72%) associated with Na⁺-independent transport. Interestingly, treatment with the cytokine increased both the K_m (43%) and V_max. (64%) of the Na⁺-dependent component. The inhibition patterns suggest the existence of more that one Na⁺-dependent transport for alanine although the majority of the amino acid is transported through the A system. The results presented suggest that, during gestation, the mother is able to adapt her placental amino acid transport systems to compensate for the nitrogen drainage associated with tumour growth and thus provide the fetus with enough amino acids to allow its normal growth, and that TNF could be responsible for the triggering of this compensatory mechanism.