Author Archives: Matrix and Metastasis

About Matrix and Metastasis

Matrix & Metastasis Lab | Targetting the Extracellular Matrix in Cancer

Publication: CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan

Thomas R. Cox, Aug 2019

CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan

We are super excited to announce that our recent work in close collaboration with A/Prof Paul Timpson has just been published in Nature Communications (view the full Open-Access article here)

In this work (which was a large international collaboration), co-led by our team and Paul Timpson’s team (also at the Garvan Institute), we show that remodeling of the stromal  tissue in and around pancreatic tumours may be the key to stopping their spread and improving chemotherapy outcomes.

Cancer cell CAF crosstalk

What we did

We already know that tumours are made up of heterogenous populations of cancer cells with different mutational landscapes. Furthermore, recently, the field has begun to realise that the cancer associated fibroblasts (CAFs) present in and around the tumour are also a diverse collection of  subpopulations.

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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: LOXL1 Is Regulated by Integrin α11 and Promotes Non-Small Cell Lung Cancer Tumorigenicity

Thomas R. Cox, May 2019

LOXL1 Is Regulated by Integrin α11 and Promotes Non-Small Cell Lung Cancer Tumorigenicity

Our lab has contributed to a recent paper by Zeltz and colleagues looking at the interplay between Lysyl Oxidase Like 1 (LOXL1) and Integrin α11 in Non-Small Cell Lung Cancer (NSCLC). The work was published in the Open-Access journal Cancers.

LOXL1, integrin a11 and ECM crosstalk

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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: 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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