News: Anti-fibrotic LOX family inhibitor program to commence Phase I trials

Thomas R Cox, Nov 2018

We’re exited to reveal that we have been working hard with Pharmaxis on the development of their lysyl oxidase (LOX) systemic inhibitor for the potential use as a stromal co-targeting agent in pancreatic cancer.

Pharmaxis has developed an oral drug that inhibits all LOX family members, and which has shown to lead to significant reductions in fibrosis (scarring) in in-vivo models of kidney fibrosis, lung fibrosis, myelofibrosis and now with our help, in models of pancreatic cancer.

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People: New starter for M&M

Thomas R. Cox, Oct 2018

We’re pleased to welcome our newest Animal Technician Michelle Yam to the team. Michelle is returning home to Australia having worked at West Virginia University in the US.Michelle Yam (Matrix and Metastasis Lab)

Michelle joins us and will take care of the welfare and maintenance of the animals used in our cancer research program to ensure we conform to the Australian Code for the Care and Use of Animals for Scientific Purposes and the New South Wales Animal Research Regulations.

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: Charting the unexplored extracellular matrix in cancer

Thomas R. Cox, Apr 2018

Charting the unexplored extracellular matrix in cancer

Our new review on the recent advances in mapping the extracellular matrix in cancer has just been published in the International Journal of Experimental Pathology.

Composed of hundreds of different building blocks, the extracellular matrix (ECM) makes up the complex, highly cross‐linked, three‐dimensional (3D) network of macromolecules (proteins, glycoproteins and its subgroup of proteoglycans, polysaccharides (glycosaminoglycans), elastins and carbohydrates) that surround cells. It is essential to correct organisation and function of all tissues and organs, yet we know remarkably little about the assembly and organisation of these supramolecular structures of the ECM. In this review we discuss some of the recent advances and technologies that are helping us delve deeper into the matrix and further our understanding of the impact that dysregulated ECM has in diseases such as cancer.

IJEP Charting the unexplored extracellular matrix in cancer

Extracellular matrix building blocks

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People: International exchange

Thomas R. Cox, Feb 2018

Our team will shortly be welcoming Sumeyra (Elvan) Kaya from the University of Groningen in the Netherlands.

Elvan KayaElvan is joining us on exchange as part of her Masters Degree program at the University of Groningen. Elvan is interested in studying more about cancer metastasis and the role that the extracellular matrix plays in this.

Her project will look into novel ways to target the lysyl oxidases. This family of enzymes is critical to cross-linking the extracellular matrix and are highly dysregulated in cancer leading to tumour progression and spread.

 

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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Publication: The interplay between extracellular matrix remodelling and kinase signalling in cancer progression and metastasis

Thomas R. Cox, Jan 2018

The interplay between extracellular matrix remodelling and kinase signalling in cancer progression and metastasis.

Our recent review discussing the role of the extracellular matrix as a critical regulator of intracellular kinase signalling has just been published in Cell Adhesion & Migration

Extracellular_Matrix_Governs_Kinase_Signalling

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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.

Publication: Three-dimensional organotypic matrices from alternative collagen sources as pre-clinical models for cell biology

Thomas R. Cox, Dec 2017

Three-dimensional organotypic matrices from alternative collagen sources as pre-clinical models for cell biology

Our new paper on alternative collagen sources for 3D organotypic cultures for use as pre-clinical models is now out in Scientific Reports

Collaroo: 3D Organotypic matrices for cancer biology

Cellular interactions with the extracellular matrix (ECM) occur in a three-dimensional (3D) context and this essential aspect of the tumour microenvironment can lead to altered sensitivity to therapeutics and even act as a barrier to their delivery. This key feature is often overlooked in pre-clinical studies and is likely one of the central factors contributing to the high attrition rates of lead compounds within the pharmaceutical industry. This organotypic platform allows assessment of lead compounds in both the stromal compartment or in a 3D co-culture setting using large scale collagen preparations from alternative sources.

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People: Jessica joins M&M

Thomas R. Cox, Dec 2017

Jessica Chitty (Matrix and Metastasis Lab)I’m delighted to announce that Jessica Chitty will shortly be joining the lab as a postdoctoral research fellow. Jessica has just completed her Ph.D at the University of Queensland and is making the move south to join our team.

Having completed a degree in Biochemistry in the UK, and her Ph.D in Australia, Jessica brings experience in investigating the translational repurposing of key anti-cancer/antimycotic targets, along with significant expertise in enzyme biochemistry and molecular biology in the context of rational drug design, focusing towards translational research.

Jessica will focus her work on our ongoing interest into the lysyl oxidase family of enzymes and their role in pancreatic cancer.