GDF10 exacerbates metastatic burden and cachexia in murine models of cancer

Metastasis and cancer-induced cachexia significantly reduce survivorship and quality of life for cancer patients. GDF10 (BMP3b) is a TGF-ß superfamily ligand with little knowledge of its role in cancer progression. Some studies have shown that GDF10 exerts tumor-suppressive effects in a range of cancer types and also plays a protective role against muscle wasting. Basal transcription of GDF10 was described previously to be downregulated in both primary tumors and cachectic muscle. Here, we set out to investigate the therapeutic potential of GDF10 in the 4T1.2 mouse model of breast cancer metastasis and in the C-26 mouse model of cancer cachexia, hypothesizing that GDF10 would ameliorate both metastatic and cachectic disease pathology. Systemic rAAV6:GDF10 administration to mice did not alter primary tumor growth; however, metastatic burden was increased in the mice bearing 4T1.2 tumors. Similarly, increased intramuscular rAAV6:GDF10 expression exacerbated skeletal muscle wasting in C-26 tumor-bearing mice. These results contradicted our initial hypothesis and highlight the complexity of signaling mechanisms utilized by BMP family ligands. Our data point to the need for more research to understand how to target GDF10 in anti-cancer therapy.