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Making a move: How cancer cells migrate out of tumours

Yamini Srikanth

Researchers from the Indian Institute of Science (IISc), Bengaluru, have built organs on chips to simulate cancer metastasis. They examined how cancer cells respond under conditions of ageing and diabetes, finding that stress enhanced metastatic potential. 

Yamini News title image
(From left to right) Ramray Bhat, Nilesh Kumar (first author), Bidita Samanta, and Prosenjit Sen. Photo Cedit: Ebinesh Abraham.

Everyone knows cancer can be deadly, but what exactly makes it so dangerous? When a cancer develops in a site in the body, it usually manifests as a tumour or a clump of cells. Cancer can also spread from its original site to other parts of the body, a process known as metastasis. This is the leading cause of cancer-related deaths, making it a critical area of study. Metastasis is mysterious enough, and it’s further complicated by background processes like inflammation and ageing. Tumours and cancer cells exist within the body, and only recent decades of research have focused on these surroundings. 

We need to look at cancer cells, and how they interact with the normal cells and tissues around them. The surrounding of cancer cells can act as a barrier to the spread. What if these barriers get weakened? One of the ways these barriers weaken is natural ageing, and diabetes.” said Ramray Bhat, corresponding author of a recent metastasis study published in Small.

Researchers from the Department of Developmental Biology and Genetics,Centre for Nano Science and Engineering, Department of Electrical and Communications Engineering, and the Department of Bioengineering at the Indian Institute of Science (IISc), Bengaluru, have worked across disciplines to investigate metastasis. The collaborative team led by Bhat and Prosenjit Sen, a microfluidics expert at CeNSE, developed a chip to understand the system. This could be vital in developing therapeutic interventions that prevent or slow down the process of metastasis. The study examined breast cancer, which is one of the most common types. 

For a cancer cell to metastasize the first step is transport into the bloodstream, a process known as intravasation. When cancer cells try to enter blood vessels, they send out signals to the cells lining these blood vessels (endothelia). They meet, and form mixed structures, like leaky blood vessels. Both the cancer cells and endothelia make these bridges. It is cooperation through chemical signalling.” said Bhat. 

The experimental setup to examine tumour intravasation. Photo Credit: Ramray Bhat.
The experimental setup to examine tumour intravasation. Photo Credit: Ramray Bhat.

It’s a microscopic process, poorly understood, and difficult to look into. The collaborative team at IISc developed a chip to simulate this exact process, breaking it down to view single cells at a time. The team took it a step further to understand how intravasation is affected by diabetes and ageing, which weakens the surroundings of cancer cells. This meant replicating a diabetic environment, with an unusual accumulation of sugary byproducts like methylglyoxal. 

The proteins in the environment around the cells are altered distinctly due to the high methyglyoxal. That prevents cancer cells from sticking to the endothelium, allowing them to move into the blood vessels much more quickly. It’s very interesting learning,” highlighted Bhat. 

The publication seems to be of high quality and breaks new ground on a very relevant topic in organ-on-a-chip models, being cancer vasculature interactions. These will be crucial for studying early steps of metastasis formation in vitro, while in vivo models remain the gold standard for such studies to date.” said Jens Puschhof, German Cancer Research Center. Puschhof was not affiliated with the study, and studies the potential of similar chip systems.

The next step for the team at IISc is to investigate where cancer cells go after they migrate. Do they end up in the heart, lungs or liver? 

It requires complex, interlinked organs-on-chips, known as body on chips. Adding drugs and examining the effects of these drugs on the spread would also inform treatment of cancer in human patients greatly, 

We would like to build more complicated chips”, concluded Bhat.