VEGFC - Vascular Endothelial Growth Factor C |Elisa - Clia - Antibody - Protein

Background:

Vascular Endothelial Growth Factor C (VEGF-C) is a protein belonging to the vascular endothelial growth factor (VEGF) family, which plays a crucial role in angiogenesis, lymphangiogenesis, and vascular permeability. VEGF-C is a potent stimulator of angiogenesis. It promotes the proliferation, migration, and tube formation of endothelial cells, leading to the sprouting and branching of new blood vessels. Angiogenesis mediated by VEGF-C is essential for various physiological processes, including embryonic development, wound healing, and tissue repair, as well as pathological conditions such as tumor growth and metastasis. VEGF-C is a key regulator of lymphangiogenesis. It binds to its receptor VEGFR-3 (vascular endothelial growth factor receptor 3) on lymphatic endothelial cells, stimulating their proliferation, migration, and sprouting to form new lymphatic vessels. Lymphangiogenesis mediated by VEGF-C is critical for the drainage of tissue fluid, immune cell trafficking, and the maintenance of tissue homeostasis. VEGF-C can also increase vascular permeability, allowing the leakage of fluid and macromolecules from blood vessels into surrounding tissues. This effect is mediated by the activation of endothelial cell junctions and the disruption of vascular barrier integrity. Increased vascular permeability induced by VEGF-C contributes to tissue edema, inflammation, and tumor progression. VEGF-C is expressed in various tissues and cell types, including endothelial cells, fibroblasts, and tumor cells. Its expression can be induced by various stimuli, including hypoxia, growth factors, cytokines, and mechanical stress.VEGF-C expression is upregulated in pathological conditions associated with increased angiogenesis and lymphangiogenesis, such as cancer, inflammation, and lymphedema. VEGF-C expression and activity are tightly regulated by multiple factors, including transcriptional regulators, growth factors, cytokines, and microRNAs. Transcription factors such as hypoxia-inducible factor 1-alpha (HIF-1α) and nuclear factor-kappa B (NF-κB) can induce VEGF-C expression in response to hypoxia or inflammatory stimuli. Proteolytic processing of pro-VEGF-C by enzymes such as furin and plasmin can generate biologically active forms of VEGF-C, enhancing its angiogenic and lymphangiogenic activities.

Protein Structure:

• Composition: VEGFC is a secreted protein, which undergoes proteolytic processing to become active.
• Domains:
• Signal Peptide: Directs the protein to the secretory pathway.
• Receptor-Binding Domain: Facilitates binding to its receptors.
• C-terminal Propeptide: Removed during proteolytic processing to activate VEGFC.

Classification and Subtypes:

• Family: VEGFC belongs to the VEGF family, which includes VEGFA, VEGFB, VEGFD, and placental growth factor (PlGF).
• Isoforms: VEGFC undergoes proteolytic processing to produce different forms, including the mature active form that can bind to its receptors with high affinity.

Function and Biological Significance:

• Lymphangiogenesis: VEGFC is critical for the development of the lymphatic system. It promotes the growth of lymphatic vessels by activating specific receptors on lymphatic endothelial cells.
• Angiogenesis: VEGFC also plays a role in blood vessel formation, though its primary function is related to the lymphatic system.
• Role in Disease:
• Lymphedema: Mutations in VEGFC or its signaling pathway can lead to primary lymphedema, a condition characterized by swelling due to impaired lymphatic function.
• Cancer: VEGFC is implicated in cancer metastasis, particularly in the spread of cancer cells through the lymphatic system. Elevated levels of VEGFC are associated with increased lymphangiogenesis and metastasis in various cancers.

Interactions:

• Receptors: VEGFC primarily binds to VEGFR-3 (FLT4) and, to a lesser extent, VEGFR-2 (KDR). These interactions are crucial for its role in lymphangiogenesis and angiogenesis.
• Proteolytic Activation: The activity of VEGFC is regulated by proteolytic processing, which converts it from a latent precursor to an active form capable of receptor binding.

Clinical Issues:

• Lymphedema: Genetic mutations affecting VEGFC or its receptors can cause hereditary lymphedema. Therapeutic approaches aim to enhance VEGFC signaling to promote lymphatic growth and function.
• Cancer Metastasis: VEGFC's role in promoting lymphangiogenesis and cancer cell dissemination through the lymphatic system makes it a target for anti-cancer therapies. Inhibitors of VEGFC or its receptors are being explored to prevent metastasis.
• Therapeutic Potential: VEGFC's ability to induce lymphangiogenesis is being investigated for therapeutic applications in conditions requiring lymphatic repair or regeneration. Additionally, VEGFC inhibitors are being developed to curb its pro-metastatic effects in cancer.

Summary:

VEGFC (Vascular Endothelial Growth Factor C) is a vital member of the VEGF family, primarily involved in the development and maintenance of the lymphatic system. It undergoes proteolytic processing to become active and interacts mainly with VEGFR-3 and VEGFR-2 receptors. VEGFC plays a crucial role in lymphangiogenesis and, to a lesser extent, angiogenesis. Dysregulation of VEGFC is linked to diseases such as lymphedema and cancer metastasis. Understanding VEGFC's functions and mechanisms provides insights into potential therapeutic applications, including the treatment of lymphatic disorders and the inhibition of cancer metastasis.