Category Archives: Breast Cancer

Publication: Targeting Lysyl Oxidase Family Meditated Matrix Cross-Linking as an Anti-Stromal Therapy in Solid Tumours

Thomas R. Cox, Jan 2021

Targeting Lysyl Oxidase Family Meditated Matrix Cross-Linking as an Anti-Stromal Therapy in Solid Tumours

Congratulations to Kaitlin and Yordanos who just had their co-first author review published in Cancers as part of a special edition on Treating the Cancer Matrix: Progress in the Identification of Potential Therapeutic Targets. Also a shout out to Rhiannon for her amazing illustrator skills and creating some beautiful figures. And finally to Jess, who as co-senior author played an instrumental role in bringing everything together.

Extracellular matrix in cancer
Remodeling of the extracellular matrix (ECM) in solid tumours. In healthy tissue, the ECM has a structured basement membrane consisting primarily of collagens IV and VI as well as a scaffolding arrangement of fibrillar collagens that are predominantly secreted by the fibroblasts. In comparison, solid tumours typically consist of more densely packed, aberrantly cross-linked fibrillar collagens resulting from the recruitment and activation of CAFs. As the level of deposition of fibrillar collagens such as collagens I, III and V increases in the tumour ECM, so too does LOX family mediated collagen cross-linking. In addition, tumour ECM results in a breakdown of the structure of the normal basement membrane.
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Publication: Stromal cell diversity associated with immune evasion in human triple‐negative breast cancer

Thomas R. Cox, Aug 2020

Stromal cell diversity associated with immune evasion in human triple‐negative breast cancer

We are excited to have been part of a recent piece of work using single cell genomics to map the different cell types present with triple negative breast cancer which has recently been published in EMBO.

The work, led by Alex Swarbrick and his team here at the Garvan uncovered four new subtypes of cells within triple negative breast cancer, which contain promising new therapeutic targets for the aggressive disease. These cells produces molecules that suppress immune cells, which may help cancer cells evade the body’s immune system, and the work could lead to a new class of therapies for triple negative breast cancer.

Breast cancer stromal cell diversity
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Publication: Plasma polymerized nanoparticles effectively deliver dual siRNA and drug therapy in vivo

Thomas R. Cox, Jul 2020

Plasma polymerized nanoparticles effectively deliver dual siRNA and drug therapy in vivo

We are delighted to have been part of an exciting study looking into the potential of a new class of multifunctional nanocarrier to deliver dual siRNA and drug therapy to breast tumours which was recently published in Scientific Reports.

The work was led by our collaborators Miguel Santos and Steven Wise from the Applied Materials Group at the University of Sydney who pioneered the development of these novel multifunctional nanocarriers.

Plasma polymerized nanoparticles for cancer treatment
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People: Our newest M&M starter – Kaitlin

Thomas R. Cox, Jan 2020

We are pleased to announce that Kaitlin Wyllie has just joined the Matrix & Metastasis team as a Research Assistant.
Kaitlin Wyllie - Matrix & Metastasis

Kaitlin recently completed her Master of Research (M.Res.) at the Department of Molecular Sciences at Macquarie University.

Kaitlin will join our projects looking at the role of the ECM in breast cancer therapy and our efforts to develop novel targeting approaches.

 

Publication: The Mini‐Organo: A rapid high‐throughput 3D coculture organotypic assay for oncology screening and drug development

Thomas R. Cox, Aug 2019

The Mini‐Organo: A rapid high‐throughput 3D coculture organotypic assay for oncology screening and drug development

Just published in Cancer Reports is our new protocol paper detailing the development of a rapid high-throughput (96wp) 3D organotypic coculture assay that is optimised for screening cancer cell and cancer-associated fibroblast response to drugs in physiologically relevant matrices.

Mini-Organo workflow

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Publication: Targeting promiscuous heterodimerization overcomes innate resistance to ERBB2 dimerization inhibitors in breast cancer

Thomas R. Cox, Mar 2019

Targeting promiscuous heterodimerization overcomes innate resistance to ERBB2 dimerization inhibitors in breast cancer

We have just published a new paper in Breast Cancer Research in collaboration with lead researcher Dr. David Croucher from the Garvan Institute, looking at how and why ERBB2 (HER2) positive breast cancer cells develop resistance to targeted therapies such as trastuzumab (Herceptin™).

Promiscuity of the ERBB2 receptor in breast cancer

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Publication: The extracellular matrix as a key regulator of intracellular signalling networks

Thomas R. Cox, Jan 2019

The extracellular matrix as a key regulator of intracellular signalling networks

Our latest review in collaboration with Dr. David Croucher  and Dr. Dirk Fey on ‘The extracellular matrix as a key regulator of intracellular signalling networks‘ has just been published as part of a special series on ‘Translating the Matrix’ in the British Journal of Pharmacology.

Extracellular matrix interplay with MAPK-JNK Signalling

Computational model of the interplay between the ECM and drug activated MAPK‐JNK signalling network.

At their simplest, cells follow a set of rules governed by their genetic code. These rules, which are executed by the protein‐based signalling networks that the genes encode, control the assimilation of information and decision‐making processes that shape a cell’s response to their surroundings.

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People: M&M 2019 Honours Students

Thomas R. Cox, Jan 2019

The Matrix and Metastasis group is excited to be welcoming two new Honours students to the team for 2019.

Yordanos Setargew (left) and Shivanjali Ratnaseelan (right) will both be joining us to spend the next 10 months in the lab as part of their UNSW Sydney, School of Medical Sciences (SoMS) Honours Program.

Yordanos Setargew Shivanjali Ratnaseelan

Yordanos will be looking at new ways to target the lysyl oxidase (LOX) family in pancreatic cancer, and Shivanjali will be looking at how the biomechanical properties of the tumour microenvironment alter breast cancer cell sensitivity to chemotherapy.

Publication: Cancer cell ability to mechanically adjust to extracellular matrix stiffness correlates with their invasive potential

Thomas R. Cox, Oct 2018

Cancer cell ability to mechanically adjust to extracellular matrix stiffness correlates with their invasive potential

Just published in Molecular Biology of the Cell is our recent paper looking at the effect of extracellular matrix stiffness on the intrinsic biomechanical properties of cancer cells. Led by Professors Janine Erler (Biotech Research & Innovation Centre) and Lene Oddershede (Niels Bohr Institute) both from the University of Copenhagen, the study combines optical tweezers–based microrheology and deformability cytometry with 3D biological models to dissect how cancer cells biomechanically interact with and respond to the stiffness of the microenvironment they are within.

Optical Tweezers Schematic for measuring intracellular viscosity

Optical Tweezers Schematic for measuring intracellular viscosity

The results show that invasive cancer cells adjust their intracellular and overall viscoelasticity to ECM density, and that cancer cell viscosity increases during invasion into 3D collagen matrices.

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People: Introducing our first PhD Student – Michael Papanicoloau

Thomas R. Cox, Sep 2018

Michael Papanicoloau - Matrix and MetastasisThe lab is excited to be welcoming our first Ph.D. student Michael Papanicoloau who has just started in the lab. Michael joins us after completing his Honours degree in Biomedical Science at UTS and the Woolcock Institute of Medical Research.

Having been awarded a prestigious UTS Research Excellence Scholarship, Michael’s Ph.D. will focus on understanding how the extracellular matrix changes over time in solid tumours, in particular breast cancer, and how these changes feed into the pathological progression of the disease at both primary and secondary sites.

 

Publication: Targeting stromal remodeling and cancer stem cell plasticity overcomes chemoresistance in triple negative breast cancer

Thomas R. Cox, July 2018

Targeting stromal remodeling and cancer stem cell plasticity overcomes chemoresistance in triple negative breast cancer

The Matrix and Metastasis lab is excited to have been part of a study led by A/Prof Alex Swarbrick and colleagues which has just been published in Nature Communications.

The work looked at the communication between breast cancer cells and surrounding non-cancer cells which are important in helping the tumour to grow. Using mouse models, and also a Phase I clinical trial, the team showed that the communication netween breast cancer cells and cancer associated fibroblasts (CAFs) in triple negative breast tumour facilitates the adoption of “stem cell-like” properties which help the tumour grow, but also to become resistant the chemotherapy. Blocking this communication slowed down tumour growth and increased the effectiveness of chemotherapy.

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Publication: Tumor endothelial marker 8 promotes cancer progression and metastasis

Thomas R. Cox, Jul 2018

Tumor endothelial marker 8 promotes cancer progression and metastasis

Our new paper has just been published in Oncotarget. In this study, we show that Tumor endothelial marker 8 (TEM8) regulates the expression of multiple genes. In particular, we observed that the most common expression changes conserved between breast and colorectal cancer are involved in regulation of the cell cycle. In line with the microarray results we show that TEM8 regulates cancer cell proliferation and primary tumor growth. Since TEM8 KO tumors presented with fewer blood vessels we hypothesize that TEM8 contributes to the regulation of angiogenesis, likely by being secreted by cancer cells to alter endothelial cell migration and thereby supporting growth of the tumor. Moreover, we confirm that TEM8 is an important player in driving tumor cell invasion and metastatic dissemination in breast cancer.

Tumor endothelial marker 8 promotes cancer progression and metastasis

Proposed mechanism behind the impact of TEM8 on breast and CRC cancer progression.

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Publication: Removing physiological motion from intravital and clinical functional imaging data

Thomas R. Cox, Jul 2018

Removing physiological motion from intravital and clinical functional imaging data

Galene is a new tool just published in eLife that can correct for physiological motion in live imaging data post-acquisition.

Galene Motion Correction Software

eLife digest

Understanding how molecules and cells behave in living animals can give researchers key insights into what goes wrong in diseases such as cancer, and how well potential treatments for these diseases work. Continue reading →

Publication: Established Models and New Paradigms for Hypoxia-Driven Cancer-Associated Bone Disease

Thomas R. Cox, Jan 2018

Established Models and New Paradigms for Hypoxia-Driven Cancer-Associated Bone Disease

Our new review on the how hypoxia is important in cancer-associated bone disease has just been published in Calcified Tissue International.

Established Models and New Paradigms for Hypoxia-Driven Cancer-Associated Bone Disease

What is Hypoxia and why is it important in cancer?

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People: Welcome to Elysse

Thomas R. Cox, Jan 2018

The Matrix and Metastasis team is excited to be shortly welcoming Elysse Filipe

Elysse FilipeElysse recently completed her Ph.D. at the Heart Research Institute (HRI) in Sydney in the Applied Materials laboratory of Dr Steve Wise.

As a biomedical engineer Elysse is interested in developing tools and systems to study the importance of the tumour microenvironment, and in particular the extracellular matrix (ECM) in tumour progression.

Elysse’s work will focus on the importance of the biomechanical properties of the ECM in Breast Cancer onset and progression.