3D printed model created to mimic cancer metastasis

Scientists have created a 3D printed model to mimic the specific conditions that stimulate the spread of cancer cells. The model, published in the magazine Life Sciences Allianceit 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 a good prognosis and live longer. However, some tumors still spread to other organs throughout the body, a process known as metastasis, which makes treatment incredibly difficult. In fact, metastatic cancers, and not the original tumor, are responsible for the majority of cancer deaths.

Studying where and when a relatively passive tumor cell acquires the ability to move and metastasize could be a game changer for cancer treatment. Unfortunately, it is virtually impossible to witness this transition directly, and as a result, there are no therapies that target this critical but understudied step in cancer progression.”

Carlos Carmona-Fontaine, associate professor of biology at New York University and lead author of the study

Most metastatic cells arise from deep crevices within tumor tissues where oxygen and nutrients are scarce. This scarcity of resources is essential to trigger metastases. However, because this shortage occurs in cells buried within hard-to-access tumor regions, it is difficult to observe directly; in patients, animal cancer models, and even other laboratory-based tumor models.

The researchers decided to address this problem by constructing a small tumor model that reproduces the specific conditions that promote the acquisition of metastatic properties in tumor cells. The model, which they named “3MIC” for 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 a unique geometry to enable imaging of these deep, nutrient-free cells in 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, which are known to associate with the tumor during the metastatic process. As a result, they were able to study how tumor cells migrate, invade and interact with these other cells under different metabolic conditions.

In his study a Life Sciences Alliance, the researchers confirmed for the first time that factors known to promote metastasis, such as low oxygen, were also relevant in 3MIC. Interestingly, their data not only confirmed this, but also suggested a mechanism where low oxygen indirectly promotes metastasis by lowering the pH of the local tumor environment and making it more acidic.

The researchers also showed that the drugs, specifically versions of the chemotherapy drug Taxol, which effectively target tumor cells under normal conditions, failed to act on resource-deprived tumor cells, so what they were saving This may suggest that the lower drug response of metastatic cancers may be due to intrinsic changes that make cells more resistant to drugs, not a 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 tumors 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, researchers are now focused on finding early signs of cancer metastasis before cells spread, which could be used as a diagnostic tool to predict metastases and test potential therapeutic targets that could disrupt this process

In addition to Carmona-Fontaine, study authors include Libi Anandi, Jeremy Garcia, Manon Ros, Libuše Janská and Josephine Liu of NYU’s Center for Genomics and 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 Sciences General Practitioners (T32GM132037-01). ).