Volume 5.22 | Jun 6

Mammary Cell News 5.22 June 6, 2013
Mammary Cell News
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The Perivascular Niche Regulates Breast Tumor Dormancy
How disseminated tumor cells (DTCs) are kept dormant, and what wakes them up, are fundamental problems in tumor biology. To address these questions, scientists used metastasis assays in mice and showed that dormant DTCs reside on microvasculature of lung, bone marrow and brain. They then engineered organotypic microvascular niches to determine whether endothelial cells directly influence breast cancer cell growth. [Nat Cell Bio] Abstract | Press Release

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PUBLICATIONS (Ranked by impact factor of the journal)


A Renewable Tissue Resource of Phenotypically Stable, Biologically and Ethnically Diverse, Patient-Derived Human Breast Cancer Xenografts
Breast cancer research is hampered by difficulties in obtaining and studying primary human breast tissue, and by the lack of in vivo preclinical models that reflect patient tumor biology accurately. To overcome these limitations, scientists propagated a cohort of human breast tumors grown in the epithelium-free mammary fat pad of SCID/Beige and NOD/SCID/IL2γ-receptor null mice, under a series of transplant conditions. [Cancer Res] Abstract

Targeting Treatment Resistant Breast Cancer Stem Cells with FKBPL and Its Peptide Derivative, AD-01, via the CD44 Pathway
Researchers explored the ability of AD-01 to target CD44 positive breast cancer stem cells (BCSCs). Mammosphere assays and flow cytometry were utilized to analyze the effect of FKBPL overexpression/knockdown and AD-01 treatment ± other anti-cancer agents on BCSCs using breast cancer cell lines, primary patient samples and xenografts. [Clin Cancer Res] Abstract

Prolactin Suppresses a Progestin-Induced CK5-Positive Cell Population in Luminal Breast Cancer through Inhibition of Progestin-Driven BCL6 Expression
Investigators report that prolactin counteracts induction of the cytokeratin-5 (CK5)-positive population by the synthetic progestin R5020 in luminal breast cancer cells both in vitro and in vivo. [Oncogene] Abstract

Deficiency of Kruppel-Like Factor KLF4 in Mammary Tumor Cells Inhibits Tumor Growth and Pulmonary Metastasis and Is Accompanied by Compromised Recruitment of Myeloid-Derived Suppressor Cells
By using a spontaneously metastatic 4T1 breast cancer mouse model and an immunodeficient NOD/SCID mouse model, the authors demonstrated that KLF4 knockdown delayed tumor development and inhibited pulmonary metastasis, which was accompanied by decreased accumulation of myeloid-derived suppressor cells in bone marrow, spleens and primary tumors. [Int J Cancer] Abstract

TLR4 Ligand/H2O2 Enhances TGF-β1 Signaling to Induce Metastatic Potential of Non-Invasive Breast Cancer Cells by Activating Non-Smad Pathways
Scientists report that the enhancement of TGF-β1 signaling is required for inducing metastatic potential of non-invasive breast cancer cells. TGF-β1 alone could not efficiently induce the sustained activation of Smad and non-Smad pathways in non-invasive breast cancer cells. TLR4 ligand and H2O2 cooperated with TGF-β1 to enhance the sustained activation of non-Smad pathways, including p38MAPK, ERK, JNK, PI3K, and NF-κB. [PLoS One] Full Article

In Vitro Analysis of Breast Cancer Cell Line Tumourspheres and Primary Human Breast Epithelia Mammospheres Demonstrates Inter- and Intrasphere Heterogeneity
Investigators surveyed sphere-forming capacity across 26 breast cell lines, immunophenotyped spheres from six luminal- and basal-like lines by immunohistochemistry and flow cytometry and compared clonogenicity between sphere, adherent and matrigel culture formats using in vitro functional assays. [PLoS One]
Full Article | Press Release

Molecular Genetic Analysis of VRK1 in Mammary Epithelial Cells: Depletion Slows Proliferation In Vitro and Tumor Growth and Metastasis In Vivo
The authors investigated the role of vaccinia-related kinase 1 (VRK1) in the growth of normal and malignant human mammary epithelial cells, and demonstrated that shRNA-mediated depletion of VRK1 slows their proliferation significantly. [Oncogenesis] Full Article

The Luminal Progenitor Compartment of the Normal Human Mammary Gland Constitutes a Unique Site of Telomere Dysfunction
Telomeres are essential for genomic integrity, but little is known about their regulation in the normal human mammary gland. The authors demonstrated that a phenotypically defined cell population enriched in luminal progenitors is characterized by unusually short telomeres independently of donor age. [Stem Cell Rep] Abstract | Press Release


Randomized Phase II Study of the Anti–Epidermal Growth Factor Receptor Monoclonal Antibody Cetuximab with Cisplatin versus Cisplatin Alone in Patients with Metastatic Triple-Negative Breast Cancer
Epidermal growth factor receptor is overexpressed in metastatic triple-negative breast cancers, an aggressive subtype of breast cancer. The authors’ randomized phase II study investigated cisplatin with or without cetuximab in this setting. Patients who had received no more than one previous chemotherapy regimen were randomly assigned on a 2:1 schedule to receive no more than six cycles of cisplatin plus cetuximab or cisplatin alone. [J Clin Oncol] Abstract

Prospective Observational Study of Breast Cancer Treatment Outcomes for UK Women Aged 18-40 Years at Diagnosis: The POSH Study
Between 2000 and 2008, 2956 patients aged 40 years or younger were recruited to a UK multicenter prospective observational cohort study (POSH). Details of tumor pathology, disease stage, treatment received, and outcome were recorded. Overall survival and distant disease-free interval were assessed using Kaplan-Meier curves. [J Natl Cancer Inst] Abstract | Press Release

Air-Liquid Interface Culture for Respiratory Research: Watch Q&A Video

Targeted Therapy for HER2 Positive Breast Cancer
This article reviews the data presented at 2012 American Society of Clinical Oncology and 2012 San Antonio Breast Cancer Symposium regarding progress made in the field of HER2 positive breast cancer and examines the future of HER2 targeted therapy. [J Hematol Oncol] Abstract

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Results of New Analysis Support Use of NanoString’s Prosigna™ Assay to Help Identify Node-Positive Early-Stage Breast Cancer Patients at Low Risk of Recurrence
NanoString Technologies, Inc. announced new results from the combined data analysis of the Austrian Breast & Colorectal Cancer Study Group 8 and Arimidex, Tamoxifen, Alone or in Combination studies. The results indicated that NanoString’s Prosigna Breast Cancer Assay can be used to help identify node-positive early-stage breast cancer patients who are at low risk of recurrence. [Press release from NanoString Technologies, Inc. discussing research presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

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Oncothyreon and Array Announce Collaboration to Develop and Commercialize Anti-HER2 Compound ARRY-380
Oncothyreon Inc. and Array BioPharma Inc. announced that they will collaborate to develop and commercialize ARRY-380, an orally active, reversible and selective small-molecule HER2 inhibitor. Array previously completed a Phase I clinical trial of ARRY-380 in patients with heavily pre-treated metastatic breast cancer which demonstrated that the compound was well tolerated and had anti-tumor activity. [Oncothyreon Inc.] Press Release

New Technology Makes Breast Cancer Surgery More Precise at UC Irvine

Surgeons at UC Irvine Medical Center are the first in the country to use a device that reduces by half the need to reoperate and cut out breast cancer cells missed during an initial lumpectomy. The MarginProbe System lets the surgeon immediately assess whether cancer cells remain on the margins of excised tissue. Currently, patients have to wait days for a pathologist to determine this. [UC Irvine Medical Center] Press Release


National Institutes of Health (United States)

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)


NEW Cell Signaling in Metabolism, Inflammation and Cancer
September 2-6, 2013
Suzhou, China

NEW Global Breast Cancer Conference 2013
October 10-12, 2013
Seoul, Korea

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NEW PhD Studentship – Breast Cancer Biology (Royal College of Surgeons in Ireland)

Postdoctoral Position – Breast and Ovarian Cancer Biology (University of Pennsylvania School of Medicine)

NEW Director of Cell Processing Facility (S L Collins Associates, Inc.)

Postdoctoral Position – Breast Cancer/Stem Cell Biology (UC College of Medicine)

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

Postdoctoral Fellow – Cancer Genes in Breast Cancer (MD Anderson Cancer Center)

Postdoctoral Fellow – Stem Cell and Cancer Biology (Johns Hopkins University School of Medicine)

Postdoctoral Fellow – Breast Cancer Cell Research (Mount Sinai School of Medicine)

Research Associate – Breast Cancer Biology (University of North Carolina at Charlotte, Department of Biology)

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