MiR-210 Is Overexpressed in Tumor-infiltrating Plasma Cells in Triple-negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous group of breast cancer and is characterized by aggressiveness and poor prognosis. MicroRNA represents a new class of biomarkers, and accumulating evidence indicates that microRNAs contribute to tumorigenesis and cancer metastasis. It has been described that miR-210 is highly expressed in TNBC, and its overexpression had been linked to poor prognosis. In a previous work, we showed that in TNBC miR-210 is expressed in tumor cells and also in the tumor microenvironment (TME), particularly in inflammatory CD45-LCA positive cells. However, the exact identity of these cells remained unknown. In this study, we performed in situ hybridization and immunohistochemistry using validated antibodies for the different specific immune cell markers on adjacent sections of 23 TNBC infiltrated with immune cells. We found that miR-210 expressing cells in the TME were stained positive with CD79a, a B-cell lineage marker. These tumor-infiltrating cells were negative for CD20 and Ki-67 but positive for MUM1 and CD38 and also expressed immunoglobulins, indicating that they are immunoglobulin-producing plasma cells (PCs). To the best of our knowledge, this is the first study demonstrating miR-210 expression in tumor-infiltrating PCs.

Silencing of casein kinase 1 delta reduces migration and metastasis of triple negative breast cancer cells.

The casein kinase 1 delta (CSNK1D) is a conserved serine/threonine protein kinase that regulates diverse cellular processes including cell cycle progression, circadian rhythm, and neurite outgrowth. Aberrant expression of CSNK1D is described in several cancer types including breast cancer, where it is amplified in about 30% of triple negative breast (TNBC). Here, we have investigated the function of CSNK1D in triple negative cancer cell migration and metastasis. By using immunohistochemistry and in situ hybridization, we found that CNSK1D is highly expressed in primary tumor cells and in tumor cells invading lymphatic nodes compared to non-metastatic tumors. In vitro, knock-down of CSNK1D expression with specific shRNAs in the breast cancer cell line MDA-MB-231 markedly inhibited cancer cell proliferation, invasion and migration and affected the expression of the tight junction proteins claudin 1, occludin and the junction adhesion molecule A. In vivo, the inactivation of CSNK1D reduced lung metastasis in MDA-MB-231 breast cancer xenografts. Altogether, our results indicate that the downregulation of CSNK1D expression inhibits the proliferation and reduces the migration and the metastasis of breast cancer cells. As numerous inhibitors of CSNK1D are currently under development, this might represent an attractive therapeutic target for the treatment of TNBC.

DNA methylation profiling reveals a predominant immune component in breast cancers.

Breast cancer is a molecularly, biologically and clinically heterogeneous group of disorders. Understanding this diversity is essential to improving diagnosis and optimizing treatment. Both genetic and acquired epigenetic abnormalities participate in cancer, but the involvement of the epigenome in breast cancer and its contribution to the complexity of the disease are still poorly understood. By means of DNA methylation profiling of 248 breast tissues, we have highlighted the existence of previously unrecognized breast cancer groups that go beyond the currently known 'expression subtypes'. Interestingly, we showed that DNA methylation profiling can reflect the cell type composition of the tumour microenvironment, and in particular a T lymphocyte infiltration of the tumours. Further, we highlighted a set of immune genes having high prognostic value in specific tumour categories. The immune component uncovered here by DNA methylation profiles provides a new perspective for the importance of the microenvironment in breast cancer, holding implications for better management of breast cancer patients.