<i>Drosophila</i> storage proteins promote both the rate and the duration of tumor growth.

Abstract

Amino acid storage proteins, such as serum albumin in mammals, are known to accumulate within tumors, but their precise contribution to tumor biology remains unclear. Using both cachectic and noncachectic tumor models in <i>Drosophila</i>, we observed that fat body-derived hexamerins accumulate in the tumors through a selective uptake process. Disabling this uptake led to a marked reduction in tumor growth, demonstrating that hexamerins are used as a nutrient source to support cancer progression. Hexamerin uptake also supports expression of the relaxin-like <i>Drosophila</i> insulin-like protein 8 (Dilp8) by the tumor, inhibiting ecdysone production and extending the growth period. This coupling between nutrient uptake by the tumor and inhibition of the developmental progression exerts a full diversion of the host resources. Functional parallels with mammalian albumins suggest evolutionarily conserved mechanisms with potential implications for cancer biology.