Mammary Cell News Volume 7.10 | Mar 19 2015

The Chemokine Receptor CCR7 Promotes Mammary Tumorigenesis through Amplification of Stem-Like Cells
CCR7 was found to exert its function by regulating mammary cancer stem-like cells in both murine and human tumors. In vivo experiments showed that loss of CCR7 activity either through deletion or pharmacological antagonism significantly decreased functional pools of stem-like cells in mouse primary mammary tumors, providing a mechanistic explanation for the tumor-promoting role of this chemokine receptor. [Oncogene] Abstract

Regulation of Anti-Apoptotic Signaling by Kruppel-Like Factors 4 and 5 Mediates Lapatinib Resistance in Breast Cancer
In primary human breast cancers, investigators observed a positive correlation between KLF4/5 transcript abundance, particularly in the human epidermal growth factor receptor 2-enriched subtype. Furthermore, KLF4/5 protein was rapidly upregulated in human breast cancer cells following treatment with the HER2/epidermal growth factor receptor inhibitor, lapatinib. [Cell Death Dis] Full Article

Characterization of Macrophage – Cancer Cell Crosstalk in Estrogen Receptor Positive and Triple-Negative Breast Cancer
Scientists performed whole transcriptome sequencing of human monocytes that were co-cultured with estrogen receptor positive or triple-negative breast cancer cell lines and studied the biological responses related to the differential gene activation in both monocytes and cancer cells by pathway analysis. [Sci Rep] Full Article

ANGPTL2 Increases Bone Metastasis of Breast Cancer Cells through Enhancing CXCR4 Signaling
Researchers show that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) increases responsiveness of breast cancer cells to CXCL12 by promoting up-regulation of CXCR4 in those cells. [Sci Rep] Full Article

FOXA2 Attenuates the Epithelial to Mesenchymal Transition by Regulating the Transcription of E-Cadherin and ZEB2 in Human Breast Cancer
Researchers found that forkhead box A2 (FOXA2) prevented the epithelial to mesenchymal transition in human breast cancer. They observed a strong correlation between the expression levels of FOXA2 and the epithelial phenotype. [Cancer Lett] Abstract

Pnck Overexpression in HER-2 Gene-Amplified Breast Cancer Causes Trastuzumab Resistance through a Paradoxical PTEN-Mediated Process
The frequency of pregnancy up-regulated non-ubiquitous calmodulin kinase (Pnck) expression in HER-2-amplified breast cancer was examined by immunohistochemistry, and the impact of Pnck expression in the presence of HER-2 amplification on cancer cell proliferation, clonogenicity, cell-cycle progression, and Trastuzumab sensitivity was examined in vitro by transfection of cells with Pnck. [Breast Cancer Res Treat] Abstract

A Membrane-Type-1 Matrix Metalloproteinase (MT1-MMP) – Discoidin Domain Receptor 1 Axis Regulates Collagen-Induced Apoptosis in Breast Cancer Cells
To address the impact of type I collagen on the fate of tumor cells, human breast carcinoma MCF-7 cells were cultured within three-dimensional type I collagen gels (3D COL1). They performed a transcriptomic analysis to decipher the molecular mechanisms regulating 3D COL1-induced apoptosis in human breast cancer cells. [PLoS One] Full Article

CLINICAL RESEARCH

TBCRC 019: Phase II Trial of Nab-PAC with/without the Anti-Death Receptor 5 Monoclonal Antibody Tigatuzumab in Patients with Triple Negative Breast Cancer
Tigatuzumab (TIG) has strong in vitro/in vivo activity against basal-like breast cancer cells enhanced by chemotherapy agents. This study evaluates activity of TIG and chemotherapy in patients with metastatic triple negative breast cancer. [Clin Cancer Res] Abstract

Antiangiogenic Therapy in Recurrent Breast Cancer with Lymphangitic Spread to the Chest Wall: A Randomized Phase II Trial of Bevacizumab with Sequential or Concurrent Oral Vinorelbine and Capecitabine
Scientists assessed efficacy of bevacizumab in combination with oral chemotherapy in patients with breast cancer with lymphangitic spread to the chest wall and identified surrogate biomarkers of response to bevacizumab. [Breast] Abstract

The Novel Role of miRNAs for Tamoxifen Resistance in Human Breast Cancer
The authors review the miRNAs involved in regulation of tamoxifen resistance in human breast cancer and the mechanism of how the modulation of miRNAs may regulate the sensitivity of breast cancer cells to tamoxifen. They also discuss the future prospects of studies about miRNAs in regulation of tamoxifen resistance and miRNA-based therapeutics for tamoxifen resistance breast cancer patients. [Cell Mol Life Sci] Abstract

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Etirinotecan Pegol (NKTR-102) Prolonged Median Overall Survival by 2.1 Months versus Active Control in Patients with Advanced Breast Cancer in Phase III Study; Trial Did Not Achieve Statistical Significance (p=0.08)
Nektar Therapeutics announced topline results from its Phase III BEACON study evaluating single-agent NKTR-102 in patients with advanced breast cancer. BEACON compared NKTR-102 to an active control arm comprised of a single chemotherapy agent of physician’s choice in patients who were heavily pre-treated with a median of three prior therapies for metastatic disease. [Nektar Therapeutics] Press Release

Fred Hutch Unleashes Powerful Databases with Launch of Argos
The Fred Hutchinson Cancer Research Center, in conjunction with LabKey Software, has developed and launched Argos, an application that provides the interface and analytical power that researchers and clinicians will use to search for important patterns in cancer development, progression and treatment response. [Fred Hutchinson Cancer Research Center] Press Release

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Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Gene Regulation in Breast Cancer/Stem Cell Biology (University of Cincinnati College of Medicine)

Postdoctoral Fellow – Cancer/Breast Cancer Genomic Instability and Cell Biology (University of Queensland)

Research Associate – Division of Cancer Studies (King’s College London)

Clinician Scientist (National University of Singapore)

Postdoctoral Fellow – Stem Cells and Breast Cancer (Albert Einstein College of Medicine)

Director – Vector Production (Sangamo BioSciences, Inc.)

Senior Process Development Engineer (Sangamo BioSciences, Inc.)

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