Abstract #2049

Background: Metastasis involves processes such as invasion, angiogenesis, intravasation, extravasation and eventual proliferation in the target organ. Metastasis initiation genes are those involved in dissemination of cells from the primary tumor while metastasis virulence genes contribute to metastatic colonization, specifically at the secondary site. Identification of metastasis initiation and virulence genes is critical to improve our understanding of and the ability to effectively treat metastatic breast cancer.
 Methods: A 51-gene signature was previously identified using RNA from 20 primary breast and matched metastatic lymph node tumors using the U133 2.0 microarrays (Affymetrix). Real-time PCR was performed for each assay using TaqMan assays (Applied Biosystems) using RNA from 25 pairs of primary breast and matched metastatic lymph node tumors. Data was evaluated using Mann-Whitney testing.
 Results: Gene expression levels were significantly different for 40 genes including 25 with P<0.001 and 15 with P<0.05. Thirteen of these genes had significantly higher levels and 27 had lower levels of expression in metastatic tumors. Ten genes had >50-fold difference in expression including WNT2, KRT14, TAC1, COL11A1, MMP13, GRP, and KERA with higher expression in primary tumors and EPHA3, PAX5 and NTS with higher expression in the metastasis.
 Discussion: A breast cancer metastasis signature involving 40 genes has been identified and validated. Genes expressed at higher levels in primary breast tumors are largely involved in degradation of the extracellular matrix (ECM), likely enabling cells with metastatic potential to disseminate. Decreased expression of these genes in the metastatic tumors suggests that once tumor cells have disseminated, invasion into foreign tissues does not require active tissue remodeling. Rather, cells that have successfully metastasized are characterized by the expression of genes involved in transcription, metabolism and immune response, potentially blocking cellular differentiation and providing cells with proliferation and survival advantages. These data not only improve our understanding of the biological processes involved in successful metastatic but provide new targets to arrest tumor cells dissemination and metastatic colonization.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2049.

Thirty-first San Antonio Breast Cancer Symposium Dec 10-14, 2008; San Antonio, TX