Abstract
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.
Highlights
We previously reported that the secreted factors interleukin 6 (IL6), CSF2, CC-chemokine ligand 5 (CCL5), vascular endothelial growth factor A (VEGFA), and VEGFC are pivotal orchestrators of basal breast cancer growth and metastasis[4,12]
We demonstrated a crosstalk between basal breast cancer cells and blood endothelial cells (BEC)/lymphatic endothelial cells (LEC) that was important for primary tumor growth[12]
We showed that the secretomes of the BEC and LEC are perturbed in distinct ways, influencing primary tumor growth, pericyte infiltration, and angiogenesis in different ways[12]
Summary
We previously reported that the secreted factors IL6, CSF2, CCL5, VEGFA, and VEGFC are pivotal orchestrators of basal breast cancer growth and metastasis[4,12] This previous study reported that basal breast cancer cells secrete interleukin 6 (IL6), a cytokine, which conditions (educates, reprograms) lymphatic endothelial cells (LEC) within pre-metastatic organs and primary tumors to secrete the chemokine CC-chemokine ligand 5 (CCL5) and the growth factor, vascular endothelial growth factor A (VEGFA)[4]. In addition to having a pivotal role in basal breast cancer growth and metastasis, the secreted factors implicated in our previous study (IL6, CSF2, CCL5, VEGFA, and VEGFC) may serve critical roles in other subtypes of breast cancers. The goals of this study are: (a) to understand how these key pro-metastatic factor genes are expressed in breast cancer subtypes, (b) to examine how their associated receptor genes are expressed in the subtypes, and (c) to evaluate whether these gene expression profiles can predict the survival rates within each breast cancer subtype
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