Scientists have been trying to understand how cancer cells manage to invade the blood vessels and escape from the primary site. Now, a new research from the Josep Carreras Institute in Spain has identified a key protein that regulates the growth and remodeling of blood vessels, and how it is altered in cancer.
The Role of VEGF-C in Angiogenesis and Lymphangiogenesis
The protein is called vascular endothelial growth factor C (VEGF-C), and it belongs to a family of molecules that stimulate the formation of new blood vessels (angiogenesis) and lymphatic vessels (lymphangiogenesis). These processes are essential for normal development, wound healing, and immune response, but they can also be hijacked by cancer cells to promote their survival and dissemination.
VEGF-C is produced by various cell types, including cancer cells, and it binds to specific receptors on the surface of endothelial cells, the cells that line the inner walls of blood vessels and lymphatic vessels. By activating these receptors, VEGF-C triggers a cascade of signals that instruct the endothelial cells to proliferate, migrate, and form new branches.
VEGF-C is produced by various cell types, including cancer cells, and it binds to specific receptors on the surface of endothelial cells, the cells that line the inner walls of blood vessels and lymphatic vessels. By activating these receptors, VEGF-C triggers a cascade of signals that instruct the endothelial cells to proliferate, migrate, and form new branches.
How VEGF-C Is Altered in Cancer
The researchers, led by Dr. Francesc Viñals, analyzed the expression and function of VEGF-C in different types of cancer, including breast, lung, colon, and skin cancer. They found that VEGF-C levels were increased in most of the tumors, and that this was associated with a worse prognosis and a higher risk of metastasis.
They also discovered that VEGF-C was not only produced by cancer cells, but also by other cells in the tumor microenvironment, such as fibroblasts, macrophages, and mast cells. These cells secrete VEGF-C in response to inflammatory signals, creating a positive feedback loop that enhances the angiogenic and lymphangiogenic activity of VEGF-C.
Moreover, the researchers found that VEGF-C was modified by a process called glycosylation, which involves the addition of sugar molecules to the protein. This modification increased the stability and activity of VEGF-C, making it more potent and resistant to degradation.
They also discovered that VEGF-C was not only produced by cancer cells, but also by other cells in the tumor microenvironment, such as fibroblasts, macrophages, and mast cells. These cells secrete VEGF-C in response to inflammatory signals, creating a positive feedback loop that enhances the angiogenic and lymphangiogenic activity of VEGF-C.
Moreover, the researchers found that VEGF-C was modified by a process called glycosylation, which involves the addition of sugar molecules to the protein. This modification increased the stability and activity of VEGF-C, making it more potent and resistant to degradation.
The Potential of Targeting VEGF-C for Cancer Therapy
The findings of the study, published in the journal Nature Communications, suggest that VEGF-C is a key player in the vascularization and metastasis of cancer, and that targeting it could be a promising strategy to stop cancer from spreading.
The researchers tested the effect of blocking VEGF-C in mouse models of breast and lung cancer, using antibodies that bind to VEGF-C and prevent it from activating its receptors. They found that this treatment reduced the growth and vascularization of the primary tumors, as well as the formation of metastases in the lungs and lymph nodes.
The researchers also explored the possibility of inhibiting the glycosylation of VEGF-C, using a drug that interferes with the enzyme that adds the sugar molecules to the protein. They found that this drug reduced the stability and activity of VEGF-C, and also impaired the angiogenic and lymphangiogenic response of the tumors.
The study demonstrates that VEGF-C is a crucial factor for the vascularization and metastasis of cancer, and that interfering with its production, function, or modification could be a novel way to combat cancer progression. The researchers hope that their findings will pave the way for the development of new therapies that target VEGF-C and its signaling pathways, and that these therapies will improve the survival and quality of life of cancer patients.
The researchers tested the effect of blocking VEGF-C in mouse models of breast and lung cancer, using antibodies that bind to VEGF-C and prevent it from activating its receptors. They found that this treatment reduced the growth and vascularization of the primary tumors, as well as the formation of metastases in the lungs and lymph nodes.
The researchers also explored the possibility of inhibiting the glycosylation of VEGF-C, using a drug that interferes with the enzyme that adds the sugar molecules to the protein. They found that this drug reduced the stability and activity of VEGF-C, and also impaired the angiogenic and lymphangiogenic response of the tumors.
The study demonstrates that VEGF-C is a crucial factor for the vascularization and metastasis of cancer, and that interfering with its production, function, or modification could be a novel way to combat cancer progression. The researchers hope that their findings will pave the way for the development of new therapies that target VEGF-C and its signaling pathways, and that these therapies will improve the survival and quality of life of cancer patients.
Sources: scitechdaily.com | medicalxpress.com | eurekalert.org | news-medical.net