Molecular response of the axillary lymph node microenvironment to metastatic colonization

Breast stroma plays an active role in tumorigenesis, undergoing both phenotypic and molecular changes that facilitate and promote tumor development and growth. The metastatic microenvironment also plays a role in successful colonization; however, genetic changes in these secondary microenvironments are not well described. To improve understanding of molecular changes associated with metastatic colonization, gene expression patterns from lymph node tissues from women with at least one positive, as well as one negative node, were compared. Lymph node tissue was microdissected and hybridized to U133A 2.0 gene expression arrays. Differential expression was detected using Partek(®) Genomics Suite™ 6.6 with FDR <0.05 and >2-fold change defining significance. Twenty-two genes were differentially expressed, 14 genes, including AZGP1, FOXA1 and PIP, were expressed at significantly higher levels in colonized lymph nodes and eight genes, such as CXCL2 and HPGDS, were expressed at significantly higher levels in non-metastatic lymph nodes. Thus, lymph node tissues harboring metastases have different gene expression patterns from those without metastases. Many differentially expressed genes are involved in cellular proliferation and survival, immune function and mesenchymal-epithelial transition, suggesting that repression of immune response and restoration of an epithelial phenotype in the host tissue are critical for successful establishment of lymph node metastases.