Mammary Cell News Volume 6.38 | Oct 2 2014

A Breast Cancer Stem Cell Niche Supported by Juxtacrine Signaling from Monocytes and Macrophages
The interactions between cancer stem cells (CSCs) and their surrounding microenvironment are poorly understood. Researchers show that tumor-associated monocytes and macrophages create a CSC niche through juxtacrine signaling with CSCs. [Nat Cell Biol] Abstract

A 3D Matrix Platform for the Rapid Generation of Therapeutic Anti-Human Carcinoma Monoclonal Antibodies
An experimental platform was established in which human breast cancer cells were embedded in 3D aldimine cross-linked collagen matrices and used as an immunogen to generate monoclonal antibody libraries. In turn, cancer-cell-reactive antibodies were screened for their ability to block carcinoma cell proliferation within collagen hydrogels that mimic the in vivo environment. [Proc Natl Acad Sci USA] Abstract | Full Article | Press Release

ICAM-1 as a Molecular Target for Triple Negative Breast Cancer
The authors describe the overexpression of intercellular adhesion molecule-1 (ICAM-1) in human triple negative breast cancer (TNBC) cell lines and tissues, and demonstrate that ICAM-1 is a potential molecular target and biomarker for TNBC therapy and diagnosis. [Proc Natl Acad Sci USA] Abstract

Anticipatory Estrogen Activation of the Unfolded Protein Response Is Linked to Cell Proliferation and Poor Survival in Estrogen Receptor α-Positive Breast Cancer
Investigators show that estrogen, acting via estrogen receptor α (ERα), induces rapid anticipatory activation of the unfolded protein response, resulting in increased production of the antiapoptotic chaperone BiP/GRP78, preparing cancer cells for the increased protein production required for subsequent estrogen-ERα-induced cell proliferation. [Oncogene] Abstract | Press Release

NOTCH1 Activation in Breast Cancer Confers Sensitivity to Inhibition of SUMOylation
Investigators report a selective interaction between the NOTCH1 signaling pathway and the SUMOylation cascade. Knockdown of the E2-conjugating enzyme UBC9 as well as inhibition of the E1-activating complex SAE1/UBA2 using ginkgolic acid impaired the growth of NOTCH1-activated breast epithelial cells. [Oncogene] Abstract

The Activation of G Protein-Coupled Receptor 30 (GPR30) Inhibits Proliferation of Estrogen Receptor-Negative Breast Cancer Cells In Vitro and In Vivo
GPR30, which mediates non-genomic signaling of estrogen to regulate cell growth, is highly expressed in estrogen receptor (ER)⁻ breast cancer cells. Researchers show that activation of GPR30 by the receptor-specific agonist G-1 inhibited the growth of ER⁻ breast cancer cells in vitro. [Cell Death Differ] Full Article

TGF-β-Induced Epithelial-to-Mesenchymal Transition Proceeds through Stepwise Activation of Multiple Feedback Loops
Investigators systematically measured the changes in the abundance of proteins, mRNAs, and microRNAs that represent the core regulators of epithelial-to-mesenchymal transition induced by transforming growth factor-β1 (TGF-β1) in the human breast epithelial cell line MCF10A at the population and single-cell levels. [Sci Signal] Abstract

HER-3 Peptide Vaccines/Mimics and Combined Therapy with IGF-1R, HER-2, and HER-1 Peptides Induces Effective Anti-Tumor Effects In Vitro and In Vivo and Inhibit Breast and Pancreatic Cancer Cells
Scientists show that human epidermal growth factor receptor 3 (HER-3) vaccine antibodies and HER-3 peptide mimics induce anti-tumor responses: inhibition of cancer cell proliferation, inhibition of receptor phosphorylation, induction of apoptosis and antibody dependent cellular cytotoxicity. [OncoImmunology]
Full Article | Press Release

Significance of Glioma-Associated Oncogene Homolog 1 (GLI1) Expression in Claudin-Low Breast Cancer and Crosstalk with the Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NFκB) Pathway
High GLI1 expression is a property of claudin-low cells and tumors and correlates with markers of epithelial to mesenchymal transition and breast cancer stem cells. Knockdown of GLI1 expression in claudin-low cell lines resulted in reduced cell viability, motility, clonogenicity, self-renewal, and reduced tumor growth of orthotopic xenografts. [Breast Cancer Res] Abstract | Full Article

CLINICAL RESEARCH

Phase I/II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Patients with Locally Advanced or Metastatic Breast Cancer
Investigators studied the antibody-drug conjugate glembatumumab vedotin which consists of a fully human anti-glycoprotein NMB monoclonal antibody, conjugated via a cleavable linker to monomethyl auristatin E. [J Clin Oncol] Abstract

A Phase II Study of Medroxyprogesterone Acetate in Patients with Hormone Receptor Negative Metastatic Breast Cancer: Translational Breast Cancer Research Consortium Trial 007
Preclinical data suggest that medroxyprogesterone acetate (MPA) has both anti-metastatic and anti-angiogenic activity in the absence of hormone receptors (HR). This Phase II trial assessed the activity of MPA alone or in combination with low-dose chemotherapy in patients with metastatic HR-negative breast cancer. [Breast Cancer Res Treat] Abstract

The Network of Epithelial-Mesenchymal Transition: Potential New Targets for Tumor Resistance
Investigators highlight the potential key therapeutic targets of epithelial-mesenchymal transition (EMT) linked with tumor aggressiveness, hypoxia, angiogenesis and cancer stem cells, emphasizing on an emerging EMT-associated NF-κB/HER2/STAT3 pathway in radioresistance of breast cancer stem cells. [J Cancer Res Clin Oncol] Abstract

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Data from Worldwide Trial of Two HER2-Positive Breast Cancer Drugs Shows that Trastuzumab Should Remain as Standard of Care
Analysis of more than 8,000 women who participated in the world’s largest study of two treatments for HER2-positive breast cancer reinforces other findings from the clinical trial showing that trastuzumab should remain the standard of care for this cancer. [Press release from the Mayo Clinic discussing research presented at the European Society for Medical Oncology (ESMO) 2014 Congress, Madrid] Press Release

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Breast Cancer Collaboration with the University of Southern California Norris Comprehensive Cancer Center
ANGLE plc announced it has signed a collaboration agreement with the University of Southern California Norris Comprehensive Cancer Center to investigate the clinical use of the Parsortix system for breast cancer. [ANGLE plc] Press Release

Navidea’s Lymphoseek^® Recommended by CHMP for European Approval in Sentinel Lymph Node Detection for Melanoma, Breast and Certain Head and Neck Cancers
Navidea Biopharmaceuticals, Inc. has announced that that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion recommending the granting of marketing authorization for Lymphoseek^® 250 micrograms kit for radiopharmaceutical preparation in the European Union. [Navidea Biopharmaceuticals, Inc.] Press Release

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

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Postdoctoral Research Fellow – Cell Cycle Regulatory Pathways in Breast Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Breast Cancer Research (The University of Texas MD Anderson Cancer Center)

Postdoctoral Position – Breast Cancer Research (Weizmann Institute of Science)

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

PhD Position – Breast Cancer Research (University of Iceland Biomedical Center)

Postdoctoral Positions – Cell Death of Normal Tissue Stem Cells (Sloan-Kettering Institute)

Postdoctoral Fellow – Breast Cancer Translational Research (University of Houston – College of Pharmacy)

Scientist – Mammary Cell Research (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

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