New discovery may enable accurate prediction of cancer spread before cancer develops

February 15, 2021

The researchers analysed cells, mouse models, and human patient samples using biochemical, mathematical, and biophysical methods. They identified a protein present in the mesh-like membrane structure (the basement membrane) associated with tumour and vessel softness, and good survival of cancer patients. The researchers tested if removing this protein from the basement membrane would enhance the spread of cancer, which it did, and if supply of this protein would reduce cancer spread, which it did. They proceeded to show that the levels of this protein (netrin-4) already present in basement membrane of organs may determine cancer spread even before cancer develops, in several cancer types.

"These are extremely exciting findings that open up the possibility to predict which organs a person's cancer most probably spread to before they even have cancer. This information therefore has the potential to guide and improve cancer patient treatment and care." said Professor Janine Erler, senior researcher on the paper.

In their study, the researchers could show for the first time the impact of basement membrane composition on its mechanical properties thereby affecting cancer cell transmigration over this protein border within the inter-cellular space. They identified the secreted protein netrin-4 to open nodes inside the basement membrane network, which simultaneously softens the basement membrane and increases its mesh (pore) size. This unexpected finding highlights that cancer cell movement is dominantly controlled by the basement membrane stiffness and pore size plays an underpart. Thus, the more netrin-4 inside the basement membrane of the primary tumour or inside blood vessels within organs prone to metastasis, the less metastasis, impacting on patient survival. Moreover, they demonstrate for the first time that the mechanical properties of the basement membrane independent of cancer-related modifications are a pivotal determinant of cancer patient survival.

"We were incredibly excited to find a mechanistic explanation for our observations where the theoretical modelling closely matched our experimental data. We could show that the more netrin-4 molecules present, the softer the basement membrane and the more difficult for a cell to traverse this membrane thereby keeping cells contained in one area. We are currently exploring the therapeutic and diagnostic potential of our findings. Our study is a result of a huge collaboration effort from researchers in Denmark, Sweden, Germany, the UK, and Belgium, spanning many disciplines, which has been key to obtaining the exciting results." added Dr Raphael Reuten, lead researcher on the study.

Historically, there has been much focus on the stiffness of the extracellular matrix that lies outside of cells and the influence on cancer progression. However, there have not been studies investigating the influence of basement membrane stiffness. Moreover, studying the impact of mechanical properties of the basement membrane on cell invasion and cancer metastasis has not been possible so far. The mechanistic insights into netrin-4 activity inside basement membranes has enabled the researchers to bridge this gap of knowledge and present new opportunities to study basement membrane stiffness in a broad range of biological processes.
-end-


University of Copenhagen - The Faculty of Health and Medical Sciences

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.