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Tiny tumor model recreates cancer metastasis

24 Oct 2024
Tiny tumor model recreates cancer metastasis

Scientists have created a 3D-printed model to mimic the specific conditions that spur the spread of cancer cells.

The model, published in the journal Life Science Alliance, allows researchers to study a process previously hidden from view and may open the door to new screening and treatment options for cancers at risk of spreading.

Thanks to advances in prevention, diagnosis, and treatment, many cancer patients have good prognoses and are living longer.

However, some tumours still spread to other organs throughout the body—a process known as metastasis—which makes treatment incredibly challenging.

In fact, metastatic cancers—and not the original tumour—are responsible for most cancer deaths.

“Studying the moment where and when a relatively passive tumour cell acquires the ability to move and metastasize could be a game changer for cancer treatment,” said Carlos Carmona-Fontaine, an associate professor of biology at New York University and the study’s senior author.

“Unfortunately, it is virtually impossible to directly witness this transition, and as a result, there are no therapies that target this critical but understudied step in the progression of cancer.”

Most metastatic cells arise from crevasses deep within tumour tissues where oxygen and nutrients are scarce.

This resource scarcity is essential in triggering metastases.

However, because this scarcity happens in cells buried within hard-to-reach tumour regions, it is challenging to observe directly—in patients, animal cancer models, and even in other lab-based tumour models.

The researchers decided to tackle this problem by building a tiny tumour model that replicates the specific conditions that promote the acquisition of metastatic properties in tumour cells.

The model—which they named “3MIC” for the 3D microenvironment chamber—follows the evolution of malignant cells using live microscopy, which images cells in real time.

Using 3D printing technologies, the researchers designed the model with unique geometry to allow for imaging these deep and nutrient-starved cells with unprecedented detail.

“One of the most important conditions in the emergence of metastasis—this lack of nutrients and oxygen—was also one of the most difficult to recreate and probably the most important innovation of the 3MIC,” said Carmona-Fontaine.

The 3MIC also allowed the researchers to add additional cells, such as macrophages and fibroblasts, that are known to partner with the tumour during the metastatic process.

As a result, they were able to study how tumour cells migrate, invade, and interact with these other cells under different metabolic conditions.

In their study in Life Science Alliance, the researchers first confirmed that known metastasis-promoting factors, such as low oxygen, were also relevant in the 3MIC.

Interestingly, their data not only confirmed this but also suggested a mechanism where low oxygen indirectly promotes metastasis through lowering the pH of the local tumour environment and making it more acidic.

The researchers also showed that drugs—specifically, versions of the chemotherapy Taxol—that effectively target tumour cells under normal conditions failed to act on the resource-deprived tumour cells, thus sparing them.

This may suggest that metastatic cancers’ lower drug response may be due to intrinsic changes that make cells more drug-resistant, not lower drug concentration—a distinction that was previously difficult to measure.

“In other words, the conditions we observe in the 3MIC may create an environment that protects tumours from at least some treatments, which may help us begin to explain why metastases are so difficult to treat,” said Carmona-Fontaine.

With the 3MIC in hand, the researchers are now focused on finding early signs of cancer metastasis before the cells spread, which could be used as a diagnostic tool to predict metastasis and to test possible therapeutic targets that could interrupt this process.

In addition to Carmona-Fontaine, study authors include Libi Anandi, Jeremy Garcia, Manon Ros, Libuše Janská, and Josephine Liu of NYU’s Centre for Genomics & Systems Biology.

The research was supported by the National Cancer Institute (DP2 CA250005), the American Cancer Society (RSG-21-179-01-TBE), the Pew Charitable Trust (00034121), and the National Institute of General Medical Sciences (T32GM132037-01).

Source: New York University