Gene expression profiling of circulating tumor cells and peripheral blood mononuclear cells from breast cancer patients

Abstract

Circulating tumor cells (CTCs) are cancer cells that are released from a tumor into the bloodstream. The presence of CTCs in peripheral blood has been associated with metastasis formation in patients with breast cancer. Therefore, the molecular characterization of CTCs may improve diagnostics and support treatment decisions.We performed gene expression profiling to evaluate the enriched CTCs and peripheral blood mononuclear cells (PBMCs) of breast cancer patients using an expression panel of 55 breast cancer-associated genes. The study revealed several significantly differentially expressed genes in the CTC-positive samples, including a few that were exclusively expressed in these cells. However, the expression of these genes was barely detectable in the PBMC samples. Some genes were differentially expressed in PBMCs, and the expression of these genes was correlated with tumor grade and the formation of metastasis.In this study, we have shown that the enriched CTCs of breast cancer patients overexpress genes involved in proteolytic degradation of the extracellular matrix (ECM) as well as genes that play important roles in the epithelial-mesenchymal transition (EMT) process that may occur in these cells.

Inhibition of Ca2+‐activated chloride channel ANO1 suppresses ovarian cancer through inactivating PI3K/Akt signaling

“…To further confirm the observation for ANO1 upregulation in ovarian tissues, we also isolated peripheral blood mononuclear cells (PBMCs) from patients with serous ovarian cancers and examined ANO1 mRNA expression in PBMCs in which some oncogene expressions have recently been shown to correlate with tumor grade and metastasis formation . As shown in Figure c , ANO1 mRNA expression in PBMCs was about 100‐fold higher in 9 out of 10 collected cases from serous ovarian cancer patients with an average value of 8 × 10 −3 relative to the expression of housekeeping gene ß‐actin, as compared to the value of 7.8 × 10 −5 for noncancer patients.…”

“…Therefore there is an urgent need to identify an early diagnostic biomarker for ovarian cancer. It has recently been shown that detection of gene expression profiling in PBMCs or circulating tumor cells may improve diagnostics and help make treatment decisions for breast cancer . Cytokines such as TNF network (TNF, IL6, CXCL12) are upregulated in serous ovarian cancer cell lines caused by oncogenic mutations and abnormal signaling.…”

“…Previous investigations have shown that some gene expressions in peripheral blood mononuclear cells (PBMCs) from breast cancer patients are correlated with circulating tumor cells, tumor grade and formation of metastasis . The changes of gene expression profiles in PBMCs, in response to factors released by cancer cells, are reversible and specific to tissue types of cancers such as prostate cancer, breast cancer, lung cancer and colorectal cancer .…”

“…Previous investigations have shown that some gene expressions in peripheral blood mononuclear cells (PBMCs) from breast cancer patients are correlated with circulating tumor cells, tumor grade and formation of metastasis . The changes of gene expression profiles in PBMCs, in response to factors released by cancer cells, are reversible and specific to tissue types of cancers such as prostate cancer, breast cancer, lung cancer and colorectal cancer . A recent study has demonstrated that the gene expression level of the calcium‐activated chloride channel (CaCC) ANO1 in PBMCs is highly correlated with tumor size and differentiation of gastrointestinal stromal tumors (GIST), whereas most patients with GIST become ANO1‐negative after surgery or decline of ANO1 expression level in response to imatinib treatment .…”

Circulating tumor cells and the metastatic process: the complexity of malignancy

“…In fact, whilst they supported the correlation between CTCs, metastatic process and patient's overall-survival, to date no consensus has been established regarding biological markers to be used to identify these cells [61][62][63] . Currently, putting together different studies, among all the analyzed genes related to cell survival (IGFR1, FOXO3), the EMT process (TWIST1, SNAIL, SLUG, VIM) or tumor progression and invasion (HER2, CXCR4, uPAR, VEGFA, VEGFR, Cathepsin D) only CK19, mucin 1 (MUC1) and EpCAM result as the most accepted genes [61,[64][65][66][67][68] . In addition, it has been demonstrated that metastasis exhibit, as primary tumors, an epithelial phenotype instead of a mesenchymal one, and that, using mice models, mammary tumors can promote an apparent EMT-independent lung metastatic process [69,70] .…”