A KAIST-Yonsei joint research team has discovered that increased stiffness of the extracellular matrix of the tumor microenvironment accelerates the malignant alteration of cancer cells.
The research team, led by Professors Cheong Jae-ho of Yonsei University College of Medicine (YUCM) and Kim Pil-nam and Choi Jung-kyoon of the Korea Advanced Institute of Science and Technology (KAIST), presented a new paradigm in setting up cancer treatment strategy by identifying the effect of microenvironmental factors on tumors.
Researchers had focused on mutations in tumor cells or internal signaling pathways. Only a few studies observed how the tumor microenvironment's physical factors affect malignant tumors and treatment response development.
The research team developed an experimental model of gastric cancer similar to the human tumor’s microenvironment and saw how it develops according to the matrix stiffness.
The tumor microenvironment is a broad term for cancer cells existing in a tumor and surrounding tissue cells that affect cancer formation and progression, and the extracellular matrix that constitutes them.
The research result has shown that epigenetic changes are induced within the stiffened tumor stroma leading to the demethylation of DNA and the increase of Yes-associated protein (YAP), widely known as tumor protein.
Within stiffened tumor stroma, the YAP expression level rose by more than seven times compared to soft tissues. However, when a hardened tumor was reversed into a soft tissue, cells responded to anticancer drugs.
"We were able to conduct this study because of engineering techniques that simulate tumor microenvironment similar to that in the human body," KAIST Professor Kim said. "Technologies that mimic human diseases and innovative treatments, including physical therapy, will be developed further."
YUCM Professor Cheong said, "This is the first study, which found that the cause of the malignancy of intractable diffuse gastric cancer is due to the interaction between the tumor and physical properties."
The study, titled "Matrix stiffness epigenetically regulates the oncogenic activation of the Yes-associated protein in gastric cancer," was published in the international journal Nature Biomedical Engineering.