Publication: Proteomic Profiling of Human Prostate Cancer-associated Fibroblasts (CAF) Reveals LOXL2-dependent Regulation of the Tumor Microenvironment

Thomas R. Cox, May 2019

Proteomic Profiling of Human Prostate Cancer-associated Fibroblasts (CAF) Reveals LOXL2-dependent Regulation of the Tumor Microenvironment

A new paper has just been published revealing the role of Lysyl Oxidase Like 2 (LOXL2) in the remodelling of the prostate cancer microenvironment. The work, carried out in collaboration with lead researchers from the Cancer Program, Biomedicine Discovery Institute at Monash University has just been published in Molecular and Cellular Proteomics.

Normal Prostate Fibroblast and Cancer Associated Fibroblast proteomics

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Funding: Cancer Council NSW Project Grant

Thomas R. Cox, Mar 2019

Cancer Council NSW grants for innovative cancer research

CCNSW Logo

Great news! The Matrix & Metastasis Lab been awarded a three-year project grant from Cancer Council NSW to explore a new combination approach to treating pancreatic cancer.

The project will look at how to target the Lysyl Oxidase (LOX) family of enzymes in in pancreatic cancer with the goal of improving outcomes in patients.

Pancreatic cancer has one of the poorest survival rates of all cancer, with only 25% of people surviving one year after diagnosis and only 8% for five years. This project will look at the tissue in and around pancreatic cancers, which can affect how successful chemotherapy treatment is in a patient.

The aim is to combining biology and engineering to generate 3D models that mimic tumours, along with cutting edge imaging technology and mouse models, to investigate the potential of co-targeting the Lysyl Oxidase family together with already approved cancer drugs to improve patient outcome.

Thomas Cox CCNSW Awards Evening

Dr Thomas Cox receiving the award on behalf of the team at CCNSW’s annual Research Awards Evening.

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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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People: M&M continues to grow…

Thomas R. Cox, Jan 2019

We are looking forward to the imminent arrival of our newest member, Gretel Major who is joining the group this week.

Gretel Major (Matrix and Metastasis Lab)

Gretel is joining us a new Research Assistant (RA) in the Matrix and Metastasis team having recently completed her Bachelor of Advanced Science (Honours) degree at the University of Wollongong under the mentorship of Prof. Marie Ranson.

Gretel joins us to work on our different projects underway looking at the role of the extracellular matrix (ECM) in cancer progression, and is particularly interested in developing her translational research skills.

 

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.

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: 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.