Modeling alveolar soft part sarcomagenesis in the mouse: a role for lactate in the tumor microenvironment
Posted: Sun May 03, 2020 5:08 pm
Has this article (from 2014) already been discussed in the forum?
And/or does anyone know if there are trials for ASPS involving lactate?
Cancer Cell. 2014 December 8; 26(6): 851–862. doi:10.1016/j.ccell.2014.10.003.
Summary
Alveolar soft part sarcoma (ASPS), a deadly soft tissue malignancy with a predilection for adolescents and young adults, associates consistently with t(X;17) translocations that generate the fusion gene ASPSCR1-TFE3. We proved the oncogenic capacity of this fusion gene by driving sarcomagenesis in mice from conditional ASPSCR1-TFE3 expression. The completely penetrant tumors were indistinguishable from human ASPS by histology and gene expression. They formed preferentially in the anatomic environment highest in lactate--the cranial vault--, expressed high levels of lactate importers, harbored abundant mitochondria, metabolized lactate as a metabolic substrate and responded to the administration of exogenous lactate with tumor cell proliferation and angiogenesis. These data demonstrate lactate’s role as a driver of alveolar soft part sarcomagenesis.
And/or does anyone know if there are trials for ASPS involving lactate?
Cancer Cell. 2014 December 8; 26(6): 851–862. doi:10.1016/j.ccell.2014.10.003.
Summary
Alveolar soft part sarcoma (ASPS), a deadly soft tissue malignancy with a predilection for adolescents and young adults, associates consistently with t(X;17) translocations that generate the fusion gene ASPSCR1-TFE3. We proved the oncogenic capacity of this fusion gene by driving sarcomagenesis in mice from conditional ASPSCR1-TFE3 expression. The completely penetrant tumors were indistinguishable from human ASPS by histology and gene expression. They formed preferentially in the anatomic environment highest in lactate--the cranial vault--, expressed high levels of lactate importers, harbored abundant mitochondria, metabolized lactate as a metabolic substrate and responded to the administration of exogenous lactate with tumor cell proliferation and angiogenesis. These data demonstrate lactate’s role as a driver of alveolar soft part sarcomagenesis.