Mammary Cell News Volume 11.29 | Aug 1 2019

TOP STORY

Loss of p53 Triggers WNT-Dependent Systemic Inflammation to Drive Breast Cancer Metastasis

Using a panel of 16 distinct genetically engineered mouse models for breast cancer, scientists uncovered a role for cancer-cell-intrinsic p53 as a key regulator of pro-metastatic neutrophils. Mechanistically, loss of p53 in cancer cells induced the secretion of WNT ligands that stimulated tumor-associated macrophages to produce IL-1β, thus driving systemic inflammation. [Nature] Abstract

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CD24 Signaling through Macrophage Siglec-10 Is a Target for Cancer Immunotherapy

Researchers showed that CD24 could be the dominant innate immune checkpoint in ovarian cancer and breast cancer, and was a promising target for cancer immunotherapy. They demonstrated a role for tumor-expressed CD24 in promoting immune evasion through its interaction with the inhibitory receptor sialic-acid-binding Ig-like lectin 10, which was expressed by tumor-associated macrophages. [Nature] Abstract | Press Release

Breast Cancer Stem Cells with Tumor- versus Metastasis-Initiating Capacities Are Modulated by TGFBR1 Inhibition

Using two different identification strategies, investigators studied the overlap between metastatic stem cells and tumor-initiating cells (TICs) in the MMTV-PyMT model. Results showed that in the MMTV-PyMT model, Lin^–CD90^–ALDH^high cells retained a high tumor-initiating potential in orthotopic transplants, in contrast to Lin^–CD24⁺CD90⁺, which retained higher metastatic capacity. [Stem Cell Reports] Full Article | Graphical Abstract

Pivotal Role of AKT2 during Dynamic Phenotypic Change of Breast Cancer Stem Cells

To confirm the central role of serine/threonine kinase 2 (AKT2), the authors silenced AKT2 expression via small interfering RNA and using a chemical inhibitor, in both cancer stem cells (CSCs) and non-CSCs from different cancer cell lines. Results revealed that AKT2 inhibition effectively prevented non-CSC reversion through mesenchymal to epithelial transition, reducing invasion and colony formation ability of both, non-CSCs and CSCs. [Cancers] Abstract | Download Full Article

HER2/HER3 Regulates Lactate Secretion and Expression of Lactate Receptor mRNA through the MAP3K4 Associated Protein GIT1

Investigators demonstrated that GIT1 interacted with MAP3K4 by immunoprecipitation, while cellular lactate production and the capacity of MCF-7 cells for anchorage independent growth in soft agar were dependent on GIT1. Additionally, they showed that activation of HER2/HER3 signaling led to reduced expression of lactate receptor (GPR81) mRNA and that both GIT1 and MAP3K4 were necessary for constitutive expression of GPR81 mRNA. [Sci Rep] Full Article

Migration Rather Than Proliferation Transcriptomic Signatures Are Strongly Associated with Breast Cancer Patient Survival

Scientists experimentally measured proliferation and migration phenotypes across more than 40 breast cancer cell-lines. Based on the latter, they built and validated individual predictors of breast cancer proliferation and migration levels from the cells’ transcriptomics. [Sci Rep] Full Article

A Multiple Breast Cancer Stem Cell Model to Predict Recurrence of T_1-3, N₀ Breast Cancer

Researchers developed a prognostic model to predict recurrence based on the prevalence of breast cancer stem cells in breast cancer. Immunohistochemistry and dual-immunohistochemistry were performed to quantify the stem cells of the breast cancer patients. [BMC Cancer] Full Article

Interaction of Adipose-Derived Stromal Cells with Breast Cancer Cell Lines

Conditioned media of adipose-derived stromal cells stimulated the proliferation of breast cancer cell lines depending on the individual adipose-derived stromal cell–breast cancer cell line combination. Conditioned media of adipose-derived stromal cells differentiated into adipocytes gave a lower response, and conditioned media of fibroblasts were also active. [Plast Reconstr Surg] Abstract

Antitumor Effects of Seleno-β-Lactoglobulin on Human Breast Cancer MCF-7 and MDA-MB-231 Cells In Vitro

Scientists investigated the anti-tumor effects of Seleno-β-lactoglobulin (Se-β-Lg) and its potential mechanisms of action against human breast cancer cells. The results showed that the half-maximal inhibitory concentrations of Se-β-Lg were 40.84μg/mL for MCF-7 cells and 46.04μg/mL for MDA-MB-231 cells at 24 hours, while the compound showed no cytotoxicity to normal breast cells. [Toxicol In Vitro] Abstract

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Defining and Modulating ‘BRCAness’

The concept of ‘BRCAness’ defines the pathogenesis and vulnerability of multiple cancers. The canonical definition of BRCAness is a defect in homologous recombination repair, mimicking BRCA1 or BRCA2 loss. In turn, BRCA-deficient cells utilize error-prone DNA-repair pathways, causing increased genomic instability, which may be responsible for their sensitivity to DNA damaging agents and poly-(ADP)-ribose polymerase inhibitors. [Trends Cell Biol] Abstract

3D Printing Breast Tissue Models: A Review of Past Work and Directions for Future Work

The authors review the work that has been undertaken in hopes of generating the recognized in-demand replacement breast tissue using different types of bioprinting. They then offer suggestions for future work needed to advance this field for both in vitro and in vivo applications. [Micromachines] Full Article

Visit our reviews page to see a complete list of reviews in the mammary cell research field.

TYME Technologies Announces New Collaboration with NYU Langone to Advance TYME’s Cancer Metabolism-Based Therapy, SM-88

Tyme Technologies, Inc. announced a new research collaboration with NYU Langone Health to advance the development of innovative treatments for patients with metastatic cancers, including pancreatic cancer. The collaboration will leverage NYU Langone’s state-of-the-art technologies to help inform the development of clinical therapies, focusing on identifying potential future biomarkers or combination approaches to treat cancer. [TYME Technologies] Press Release

Novartis Kisqali Significantly Prolongs Life in Women With HR⁺/HER2^– Advanced Breast Cancer Now in Two Distinct Phase III Trials

Novartis announced Kisqali^® achieved statistically significant improvement in overall survival in the Phase III MONALEESA-3 clinical trial. This is the second Phase III clinical trial in which Kisqali combination therapy met the key secondary endpoint of overall survival at the pre-planned interim analysis. [Novartis] Press Release

Merck’s KEYTRUDA^® (Pembrolizumab) in Combination with Chemotherapy Met Primary Endpoint of Pathological Complete Response (pCR) in Pivotal Phase III KEYNOTE-522 Trial in Patients with Triple-Negative Breast Cancer (TNBC)

Merck announced that the Phase III KEYNOTE-522 trial investigating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with chemotherapy met one of the dual-primary endpoints of pathological complete response following the neoadjuvant part of the neoadjuvant/adjuvant study regimen in patients with TNBC. [Merck] Press Release

GEMoaB Announces First Patient Dosed with the Affinity-Tailored T-cell-Adaptor GEM3PSCA in a Phase I Study in PSCA-Positive Late-Stage Solid Tumors

GEMoaB GmbH announced the dosing of the first patient in a Phase I open-label, dose escalation study of GEM3PSCA, an Affinity-Tailored Adapter for T-Cells. The bispecific antibody binds to the CD3-Receptor on T-cells and prostate stem cell antigen, differentially and broadly expressed in a variety of late stage solid tumors, such as castrate-resistant prostate cancer, pancreatic and breast cancer, bladder and renal cancer as well as non-small cell lung cancer. [GEMoaB GmbH] Press Release

Lotus Pharmaceutical Launched Vinorelbine Softgel Capsule, a Generic Navelbine^®, in European Markets as the First Generic

Lotus Pharmaceutical Co., Ltd confirmed the launch of Vinorelbine 20, 30 and 80mg soft capsules in Europe. The product is a generic alternative of Pierre Fabre Médicament’s Navelbine^® indicated for treatment of advanced non-small-cell lung cancer and advanced breast cancer when other treatment is not appropriate. [Lotus Pharmaceutical Co., Ltd] Press Release

‘No One Is Immune’: Alaska’s Scientists Despair over Plan to Shrink State Universities

The University of Alaska’s governing board plans to consolidate campuses to cope with a 40% cut in state funding. [Nature News] Editorial

China’s Scientists Alarmed, Bewildered by Growing Anti-Chinese Sentiment in the United States

Scientists in China are concerned about what they see as growing anti-Chinese sentiment in the United States. They dismiss claims of a vast conspiracy to steal US intellectual property and worry that new visa restrictions, scrutiny of export of scientific devices, and US investigations of Chinese and Chinese American scientists will hinder international collaborations. That could harm both countries’ research efforts as well as global scientific progress, many say. [ScienceInsider] Editorial

Déjà Vu All Over Again: Another Year Passes without Approval of New Suppliers of Marijuana for Research

Another year has passed since the Drug Enforcement Administration said it was open to approving more suppliers of marijuana for scientific research, and another year has passed without an application being approved. The lag has increasingly frustrated scientists, advocates, and members of Congress from both parties who argue that expanding research into marijuana could lead to new medicines and help identify what health risks use presents. [STAT News] Editorial

NEW European Cancer (ECCO) Summit 2019
September 12-14, 2019
Brussels, Belgium

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Fellow – Breast Cancer (Monash University)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Breast Cancer Research (Institute of Cancer Research)

Research Officer – Tumor Progression in Breast and Prostate Cancer (Garvan Institute of Medical Research)

Scientific Officer – Breast Cancer Organoid/3D Cell Culture Facility (Institute of Cancer Research London)

Postdoctoral Fellowship – Redox Biology of Lung and Breast Cancer (Washington University School of Medicine)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

Postdoctoral Fellow – Cancer Drug Response Research (University of Texas at Austin)

Canada Research Chair – Precision and Molecular Oncology (University of Calgary)

Postdoctoral Associate – Immune Responses (The Jackson Laboratory)

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