Researchers from the German Cancer Research Center and the University of Heidelberg have looked into how lymphatic vessels serve as pathway for cancer cells. The study was just published in the journal Cancer Discovery.
Lymph vessels are responsible for carrying lymph or fluid that contains white blood cells which are essential in protecting the blood against bacteria. However, they are also the pathway that regulates metastasis or the spread of cancer cells throughout the body.
Using mice models, the team looked for ways to block the spread of cancer or tumor cells. They discovered that the antibody called Angiopoietin-2 (Ang-2) within the Angiopoietin-Tie pathway ensures the spread of cancer cells. The findings can be further developed to prevent the spread of cancer cells in humans.
Spread of Cancer Cells
Similar to healthy tissue in the body, tumors are supplied by blood vessels that transport oxygen and nutrients while lymph vessels provide fluid and cells from the immune system. Although the spread of cancer cells has been identified through the process of metastases decades ago, this is the first time that a specific pathway and blocking protein has been identified in the lymphatic vessels.
The collaborative team has also developed a model system that shows how tumors can spread in a living organism. Nicholas Gengenbacher said that their research focused on the "direct transplantation of tumor tissue from one mouse to another without prior cell culture." In the mice models, they preserved the natural tissue structure while the cancerous tumors formed functional lymphatic vessels resulting in lymphogenic metastasis.
The models revealed how cancer cells use the lymph vessels as a pathway into the lymph nodes. From there, cancer spreads to vital organs. Removing the primary tumor surgically enabled to team to mimic a typical scenario of what happens after cancer patients undergo surgery. They also proved that the removal of daughter tumors is critical for patients to survive cancer.
Pathway in the Lymph Vessels
Finding ways to prevent metastases turned the focus on lymph endothelial cells, cells within the lymph vessels. Endothelial cells are responsible for several functions of lymph and blood vessels as well as produce critical signaling molecules.
Ang-2 was discovered to be a messenger protein that plays a critical role in the survival of tumor cells in the lymph vessels. More importantly, an antibody was discovered to block Ang-2 and resulted in the death of tumor cells.
The antibody also blocked the pathway for cancer cells to spread to lymph nodes and organs. They observed that fewer daughter tumors formed in organs and the mice survived longer.
Hellmut Augustin explained that they were able to prevent the spread of tumors after surgery by blocking the Ang-2 protein. Typically, malignant cells that remain after surgery can result in a relapse of cancer. He hopes that further studies can prove that the same methods can be effective in blocking the spread of tumors in humans as well.
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