Scientists at Houston Methodist say they have invented a new, ex vivo lung cancer model that mimics the process of tumor progression. Their study (“Ex Vivo four-dimensional lung cancer model mimics metastasis”) appears online in The Annals of Thoracic Surgery.

“The 4D lung cancer model can isolate tumor cells in 3 phases of tumor progression,” wrote the investigators.” This 4D lung cancer model may mimic the biology of lung cancer metastasis and may be used to determine its mechanism and potential therapy in the future.”

The 4D model is created by removing all the cells from a vertebrate lung, leaving the enveloping matrix, which provides support for cell growth and development. The native lung matrix, once cells are removed, is further modified and placed in a bioreactor to allow for human tumor cells to grow.

Unlike other tumor models, the 4D model allows the tumor cells to form 3D nodules that grow over time. Lead investigator Min P. Kim, M.D., called an earlier version of the model “3D ex vivo.” The new model's fourth dimension is flow as the latest version incorporates the movement of fluids between lungs through blood vessels. It can also be used to study the progression of other cancers besides lung, noted Dr. Kim.

This fourth dimension allows the model to show the growth of primary tumors, the formation of circulating tumor cells (CTCs), and formation of metastatic lesions. These three steps of cancer progression aren't a part of any single in vitro or ex vivo model. And unlike in vivo models of metastasis, which often require researchers to wait months for information about metastasis progression, the 4D model can provide data in a matter of days, pointed out Dr. Kim.

The team also investigated gene expression in cancer cells during different phases of tumor progression. They found the gene signatures of experimental CTCs were associated with poor survival in lung cancer patients.

“The model allowed for the isolation of unique gene signature of circulating tumor cell phase of metastasis, which may provide a clue to the mechanism of tumor progression,” said Dr. Kim.

In future experiments, the research group will focus on the unique gene signatures of circulating tumor cells to better understand the mechanism of tumor progression. The hope is that this may provide ideas for new therapies that stop metastatic spread in patients with lung cancer.








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