Analysis of gene expression of secreted factors associated with breast cancer metastases in breast cancer subtypes (original) (raw)

Breast cancer is a heterogeneous disease, having multiple subtypes with different malignant phenotypes. The triple-negative breast cancer, or basal breast cancer, is highly aggressive, metastatic, and difficult to treat. Previously, we identified that key molecules (IL6, CSF2, CCL5, VEGFA, and VEGFC) secreted by tumor cells and stromal cells in basal breast cancer can promote metastasis. It remains to assess whether these molecules function similarly in other subtypes of breast cancer. Here, we characterize the relative gene expression of the five secreted molecules and their associated receptors (GP130, GMRA, GMRB, CCR5, VEGFR2, NRP1, VEGFR3, NRP2) in the basal, HER2 (human epidermal growth factor receptor 2) positive, luminal A, and luminal B subtypes using high throughput data from tumor samples in The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). IL6 and CCL5 gene expression are basal breast cancer specific, whereas high gene expression of GP130 was observed in luminal A/B. VEGFA/C and CSF2 mRNA are overexpressed in HER2 positive breast cancer, with VEGFA and CSF2 also overexpressed in basal breast cancer. Further study of the specific protein function of these factors within their associated cancer subtypes may yield personalized biomarkers and treatment modalities. Breast cancer is the most frequently diagnosed cancer among women in the United States 1. Primary breast tumors are divided in four main molecular subtypes: Basal (also known as, triple negative), HER2 (human epidermal growth factor receptor 2) positive, Luminal A, and Luminal B. Each of these subtypes has characteristic traits and expected patient outcome. For example, basal breast cancer is the most aggressive and metastatic subtype. Basal breast tumors do not express typical breast cancer cell receptors, such as the estrogen receptor (ER), the progesterone receptor (PR), and does not overexpress the human epidermal growth factor receptor 2 (HER2) that are activated in the other subtypes 2. Thus, current hormonal therapies and HER2 inhibition cannot be used to treat basal breast cancer. Moreover, therapeutic resistance is common when treating tumors from other subtypes with hormonal therapies 3. Therefore, new therapeutics that target additional molecular factors in breast tumors are needed. Optimal therapeutics would target the factors that promote tumor growth and metastasis resulting from interactions between cancer cells, stromal cells, and extracellular matrix. Secreted factors from each of the diverse cells in a tumor regulate inter-cellular signaling between tumor cells and the microenvironment to promote breast cancer growth and metastasis 4. Specifically, the secreted factors cytokines, chemokines, and growth factors contribute to distinct modes of metastasis and subsequent mortality 5. Cytokines represent soluble proteins secreted by mammalian cells that are important in cell signaling. Among them, cytokines related to inflammatory signals are involved