Study offers clues to how cancer spreads to the brain

Researchers used microfluidic devices to track what happens to cancer cells as they migrate and take root in the brain

5:00 AM

Author | Nicole Fawcett

A recent study provided crucial insights into the mechanism mediating brain metastasis, using state-of-the-art in-vitro microfluidic devices. Credit: Advanced NanoBiomed Research

When cancer spreads to the brain, treatment options fall off. Most of the drugs designed to target metastases do not cross the blood-brain barrier or are ineffective at treating brain metastases.

“Understanding how cancer cells thrive or fail in the brain niche could help us develop new treatments targeting these molecular processes,” said Sofia Merajver, M.D., Ph.D., the Greater Good Breast Cancer Research Professor at the University of Michigan Rogel Cancer Center.

To understand the molecular processes that influence how cancer cells pass through the blood-brain barrier, Merajver and colleagues used two microfluidic chips that mapped cancer cell migration to the brain and looked at what was happening in the blood-brain niche. Results are published in the journal Advanced NanoBiomed Research.

Using breast cancer cell lines, they found that Dkk-1, a cytokine released by the astrocytes, triggers the cancer cells to migrate. Dkk-1 is known to play a role in in Wnt signaling, a key signaling pathway linked to cancer progression.

“Crosstalk between brain niche cells and cancer cells allows invading cancer cells to permeate the blood-brain barrier. Reducing Dkk-1 levels near invading tumor cells might disrupt this crosstalk and prevent brain metastases,” said corresponding author Christopher R. Oliver, Ph.D., a post-doctoral fellow in the Merajver Lab.

Additional authors: Trisha M. Westerhof, Benjamin A. Yang, Nathan M. Merill, Joel A. Yates, Megan Altemus, Liam Russell, Anna J. Miller, Liwei Bao, Zhifen Wu, Peter J. Ulintz, Carlos A. Aguilar, Aki Morikawa, Maria G. Castro

Funding for this work is from National Institutes of Health grants UL1TR002240, T32CA009676, 1R21CA245597-01, P30CA046592, 5T32CA009676-23, CA196018, AI116482; METAvivor Foundation, and the Breast Cancer Research Foundation.

This work was supported by these Rogel Cancer Center Shared Resources: Cancer Data Science, Cell and Tissue Imaging, Flow Cytometry, Immune Monitoring.

Paper cited: “Blood-Brain Barrier Remodeling in an Organ-on-a-Chip Device Showing Dkk1 to be a Regulator of Early Metastasis,” Advanced NanoBiomed Research. DOI: 10.1002/anbr.202200036


More Articles About: Cancer: Help, Diagnosis & Treatment Brain Cancer Neurological (Brain) Conditions All Research Topics Basic Science and Laboratory Research
Health Lab word mark overlaying blue cells
Health Lab

Explore a variety of health care news & stories by visiting the Health Lab home page for more articles.

Media Contact Public Relations

Department of Communication at Michigan Medicine

[email protected]

734-764-2220

Stay Informed

Want top health & research news weekly? Sign up for Health Lab’s newsletters today!

Subscribe
Featured News & Stories person looking at test close up
Health Lab
Revolutionizing head injury care
A simple blood test is changing how emergency medicine operates.
girl hugging teddy bear with alcohol bottles on ground
Health Lab
1 in 4 kids live with parents who have alcohol or other drug problems
Children living with parents who have addiction issues, also called substance used disorder, have higher risks later in life. A new study shows 1 in 4 currently live in such households.
chess pieces yellow background one red piece on right and yellow on left weighing the balance beam down
Health Lab
Interplay between key proteins could serve as a target for cancer treatment
University of Michigan researchers have identified that the balance between two proteins—STAT3 and STAT5—is important for making tumors vulnerable to immune checkpoint therapy, and targeting STAT3 degradation is a potential novel cancer immunotherapy strategy.
red cancer cell on red background
Health Lab
Researchers identify roles of key genes in colon cancer development
Researchers used mouse models and studies of colorectal cancer tissues to show that loss of SOX9 gene promotes tumor progression and the pathway it regulates can be a potential target for future treatments.
two hearts next to each other with small figure people inside and out of it
Health Lab
How neutrophil calprotectin unmasks future atherosclerotic heart disease risk
The immune system is showing evidence of playing a roll in the emergence of atherosclerotic cardiovascular disease. A rush of neutrophils, or immune cells to the site could be an explanation for how this condition forms as well as how to prevent this heart disease in the future.
lungs beating pink and orange and yellow and white circles floating around
Health Lab
Protein found in rheumatic diseases causes inflammation in COVID-19 patients
Research on the inflammatory mediator called sCD13 has identified this molecule and its receptors as new targets for treatment of autoimmune rheumatic diseases. The data suggests that sCD13 may also be of great importance in severe complications of COVID-19.