Fatty Acids Promote 'Cancer Metastasis'

Modeling Tumor Microenvironment with 3D Culture Chip to Elucidate Cancer Metastasis Induced by Fatty Acids
Additional Confirmation via Tracking Cancer Cell Migration in Mouse Model

Cancer Cell Migration Phenomenon Induced by Adipocytes

[Asia Economy Reporter Junho Hwang] A study has found that free fatty acids secreted from adipose cells surrounding cancer exacerbate the metastasis of cancer cells. As obesity is identified as a factor that worsens cancer, this is expected to provide a new clue to elucidate the correlation between cancer cells and adipose cells. The National Research Foundation of Korea announced on the 8th that a research team led by Professor Yangsook Jeon of Seoul National University and a research team from Yokohama National University in Japan published these findings in the international journal of biomaterials, Biomaterials.

Free Fatty Acids and Cancer Metastasis

Conceptual Diagram of Fatty Acid-Hypoxia Inducible Factor Signaling Pathway and 3D Tumor Microenvironment Model

The free fatty acids focused on by the research team are fatty acids produced and secreted through lipolysis in adipose cells. They are used as an energy source for cells or utilized as signaling molecules for metabolism and growth. The research team previously revealed that free fatty acids can activate HIF-1α in cancer cells, inducing tumor malignancy. HIF-1α is a transcription factor involved in the phenomenon where cancer cells transform into mesenchymal-like cells with mobility and invasiveness.

While investigating the source supplying fatty acids to cancer cells, the research team discovered that free fatty acids influence not only tumor malignancy but also cancer metastasis.

Utilization of 3D Culture Chips to Elucidate the Relationship Between Stromal Cells and Cancer Cells

Professor Jeon Yang-sook of Seoul National University (left), Seo Ji-eun, PhD candidate at Seoul National University

The research team fabricated a 3D culture chip that allows adipose cells and cancer cells to grow in their original spherical form through direct contact, co-culturing cancer cells and adipose cells at an appropriate ratio to replicate a cancer microenvironment similar to the actual biological environment. Through this, they demonstrated that fatty acids secreted from adipose cells act as stimulators activating HIF-1α in adjacent cancer cells. They compared the density of cell clusters growing as spheroids by co-culturing various combinations of cells in a chip consisting of about 1,700 compartments (each 500 μm). When cancer cells and adipose cells were co-cultured, the density decreased by about 30%. The research team explained this as a result of active movement of cancer cells. In contrast, in chips where free fatty acids were chemically removed, cancer cell metastasis did not occur.

The research team also conducted animal experiments by injecting fatty acids into the peritoneal cavity of mouse models bearing fluorescently labeled cancer cells. It was confirmed that cancer cells in mice injected with fatty acids spread from the colon to the head. Meanwhile, in mice injected with interfering RNA fragments that inhibit HIF-1α along with fatty acids, cancer cell migration was reduced by half.

The research team expects that the 3D culture chip used in this study can be applied not only to the relationship between adipose cells and cancer cells but also to elucidate interactions between various types of stromal cells and cancer cells.

This content was produced with the assistance of AI translation services.