Breast stroma plays an active role in tumorigenesis, undergoing both phenotypic and molecular changes to facilitate and promote tumor development and growth. The metastatic microenvironment also plays a role in successful colonization; however, the genetic changes in these secondary microenvironments are not well described.To improve understanding of the molecular changes associated with metastatic colonization of a foreign tissue, gene expression data was generated from lymph node tissues from women with at least one lymph node with macrometastases and one lymph node with no detectable metastases. Lymph node tissue was microdissected and hybridized to U133A 2.0 gene expression arrays. Differential expression was detected using Partek® Genomics Suite™6.5 with P<0.001, >2-fold change defining significance. Thirty-four genes were differentially expressed, 23 genes, including EPCAM, KRT19 and MUC1, were expressed at significantly higher levels in colonized lymph nodes and 11 genes, such as CXCL2 and HPGDS, were expressed at significantly higher levels in non-metastatic lymph nodes. Thus, lymph node tissue differs in gene expression between those harboring metastatic tumors and those without metastasis. Genes expressed at higher levels in colonized lymph nodes are involved in tumorigenesis, suggesting that like the breast stromal microenvironment, the metastatic microenvironment undergoes cross-talk with the tumor cells, while genes involved in immune function are down-regulated in colonized lymph nodes, suggesting that suppression of proper immune response may be required for successful metastatic colonization.
Citation Format: Rachel E. Ellsworth, Allyson L. Valente, Jennifer L. Kane, Darrell L. Ellsworth, Craig D. Shriver. Molecular response of the axillary lymph node microenvironment to metastatic colonization. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2823. doi:10.1158/1538-7445.AM2013-2823