Cancer spreading beyond the primary tumor – a process known as metastasis – is responsible for at least two-thirds of cancer deaths. Drugs targeting the metastatic progression have largely failed, in part due to the lack of predictive models that would help identify the underlying mechanisms of metastasis.
While animal models have led to key advances in the understanding of metastasis-related mechanisms, the persistent clinical failures of drugs targeting metastatic progression suggest that the differences between human and rodent biology cannot be discounted.
In a study published on August 19 in Science Translational Medicine, Columbia Engineering professor Gordana Vunjak-Novakovic and her team report the development of a multi-organ chip that mimics how cancer cells spread from vascular flow to distant organs, the first model of cancer metastasis of its kind. The chip includes compartments with millimeter-sized engineered human bone and lung tissues, and the vascular flow that contains circulating breast cancer cells and allows the dynamic cross-talk of the tissues being colonized.
“The pressing need for developing human tissue models of metastasis has been a key motivation for our study,” said Vunjak-Novakovic, who is a University Professor at Columbia University and the Mikati Foundation Professor of Biomedical Engineering and Professor of Medical Sciences (in Medicine). “Our objective was to probe the ability of cancer cells to adhere to and traverse across endothelium [inner lining of blood vessels], and to determine their capacity to survive in the tissues they are colonizing through cell reprogramming and niche remodeling.”
The study sheds light on a critical phase of metastasis, known as organ colonization, which is difficult to study using animal models. As cancer cells break away from the original tumor, they travel through the bloodstream and settle into the tissue of distant organs. From there, these cells grow until a tumor forms in a new location. The process is highly complex, requiring the cancer cells to evade tissue defense and adapt to the specific organs they invade.
This multi-organ chip allows scientists to investigate, in detail, metastatic progression with actual patient cells and tissues, as opposed to using animal models that don’t always reflect human biology. The platform enables controlled experimentation of cancer cell-tissue interactions within organ-specific microenvironments, towards revealing molecular pathways and therapeutic targets for metastasis. To demonstrate the chip’s capabilities, Vunjak-Novakovic and her colleagues examined the colonization of circulating human breast cancer cells into bone and lung.
Source: https://www.engineering.columbia.edu/about/news/new-chip-mimics-how-cancer-spreads