A core program of gene expression characterizes cancer metastases
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Franz Hartung1, Yunguan Wang2, Bruce Aronow2 and Georg F. Weber1
1University of Cincinnati Academic Health Center, Cincinnati, OH, USA
2Computational Medicine Center, Cincinnati Children’s Hospital, Cincinnati, OH, USA
Georg F. Weber, email: firstname.lastname@example.org
Keywords: metastasis; metabolism; vascularization; extracellular matrix; ion homeostasis
Received: July 28, 2017 Accepted: August 31, 2017 Published: November 02, 2017
While aberrant expression or splicing of metastasis genes conveys to cancers the ability to break through tissue barriers and disseminate, the genetic basis for organ preference in metastasis formation has remained incompletely understood. Utilizing the gene expression profiles from 653 GEO datasets, we investigate whether the signatures by diverse cancers in various metastatic sites display common features. We corroborate the meta-analysis in a murine model. Metastases are generally characterized by a core program of gene expression that induces the oxidative metabolism, activates vascularization/tissue remodeling, silences extracellular matrix interactions, and alters ion homeostasis. This program distinguishes metastases from their originating primary tumors as well as from their target host tissues. Site-selectivity is accomplished through specific components that adjust to the target micro-environment. The same functional groups of gene expression programs are activated in the metastases of B16-F10 cells to various target organs. It remains to be investigated whether these genetic signatures precede implantation and thus determine organ preference or are shaped by the target site and are thus a consequence of implantation. Conceivably, chemotherapy of disseminated cancer might be more efficacious if selected to match the genetic makeup of the metastases rather than the organ of origin by the primary tumor.
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