Telomere shortening produces an inflammatory environment that increases tumor incidence in zebrafish
Kirsten Lex, Mariana Maia-Gil, Bruno Lopes-Bastos, Margarida Figueira, Marta Marzullo, Kety Giannetti, Tânia Carvalho, Miguel Godinho Ferreira
Abstract
Significance Cancer incidence increases exponentially in human midlife. Even though mutation accumulation in somatic tissues results in increased tumorigenesis, it is currently not understood how aging contributes to cancer. Telomeres, the ends of eukaryotic linear chromosomes, shorten with each cell division. Here, we show that telomere shortening contributes to cancer in a noncell autonomous manner. Using embryo chimeras of telomerase-deficient zebrafish generated from melanoma-prone fish, we show that tumors arise more frequently, multiply faster, and become more invasive in animals with shorter telomeres. Telomere shortening gives rise to increased senescence and systemic inflammation. We observed increased melanoma dissemination in zebrafish larvae with very short telomeres. Thus, telomere shortening similar to human aging, generates a chronic inflammatory environment that increases cancer incidence.