Talk abstracts

Talk on Saturday 10:50-11:05am submitted by David Taffany

An ets2-specific transcriptional program in tumor-associated macrophages promotes tumor metastasis

David A. Taffany (Department of Molecular and Cellular Biochemistry, Comprehensive Cancer Center, The Ohio State University), Tahera Zabuawala, Sudarshana M. Sharma, Anand Merchant (Department of Molecular and Cellular Biochemistry, Comprehensive Cancer Center, The Ohio State University), Thomas J. Rosol (Department of Veterinary Biosciences, Comprehensive Cancer Center, The Ohio State University), Gustavo Leone (Department of Molecular Genetics, Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University), Kun Huang (Department of Biomedical Informatics, Comprehensive Cancer Center, The Ohio State University), Michael C. Ostrowski (Department of Molecular and Cellular Biochemistry, Department of Molecular Genetics, Comprehensive Cancer Center, The Ohio State University)

Abstract:
Tumor associated macrophages (TAMs) have been implicated in breast cancer progression and metastasis, but relatively little is known about the genes and pathways that are involved. Ets2, a member of the ETS-family of transcription factors, is a direct target of CSF-1 signaling pathways involved in regulating macrophage functions during inflammation. Using a cre/loxP approach, we provide genetic evidence that Ets2 in TAMs specifically promotes mammary tumor metastasis. Loss of Ets2 in TAMs decreased the frequency and size of lung metastases without significantly impacting primary mammary tumor burden in three distinct metastasis models. Expression profiling of isolated tumor macrophages and chromatin immunoprecipitation assays established that Ets2 represses a set of anti-angiogenic genes. Consistent with these results, loss of Ets2 in TAMs led to both decreased angiogenesis and growth of tumor metastases. Comparison of this mouse Ets2-specific TAM expression profile with human breast cancer profiles revealed a human gene expression signature that could predict overall survival of estrogen receptor negative patients. In summary, we have identified a critical factor, Ets2, in TAMs that represses a transcriptional program to promote the growth of mammary tumor metastases in the lung.

Keywords: cancer, metastasis, ets2