GSE118942
Separation of breast cancer and organ microenvironment transcriptomes in metastases
The seed-and-soil hypothesis was described over a century ago to describe why cancer cells (seeds) grow in certain organs (soil). Since then, the genetic properties that define the cancer cells have been heavily investigated, however, the genetic mediators within the organ microenvironment that mediate successful metastatic growth are less understood. In these studies, a set of human breast cancer patient-derived xenograft (PDX) metastasis models were utilized. Mammary tumors and metastases to the liver, lung, and brain were RNA-sequenced with the goal of identifying complementary cancer and organ-specific genetic properties that mediate metastatic growth. During metastatic growth of PDXs, the genetic changes that occurred in the liver and lung microenvironment were more consistent and higher in magnitude than the cancer cell transcriptomes . Integration of the liver microenvironment gene signature into genetic data from liver metastasis autopsy samples or fine-needle aspirates revealed the contribution of the microenvironment to the metastatic transcriptome. These insights identify cancer and organ-specific genetic drivers  of metastasis. Overall design: Mammary tumors and metastases to the liver, lung, and brain were RNA-sequenced with the goal of identifying complementary cancer and organ-specific genetic properties that mediate metastatic growth.