lymphatic endothelial cell migration

Definition

Target type: biologicalprocess

The orderly movement of a lymphatic endothelial cell from one site to another in the wall of a lymphatic vessel. [GO_REF:0000091, GOC:TermGenie, PMID:25745057]

Lymphatic endothelial cell migration is a complex process essential for the development and maintenance of the lymphatic vasculature. It involves a coordinated series of events that allow lymphatic endothelial cells (LECs) to detach from existing vessels, move through the surrounding extracellular matrix, and integrate into new lymphatic vessels.

**1. Initiation:**
* **Growth Factors and Cytokines:** LEC migration is triggered by a variety of growth factors and cytokines, such as vascular endothelial growth factor (VEGF)-C and VEGF-D, which bind to their respective receptors VEGFR-3 and VEGFR-2 on LECs. These signaling pathways activate downstream signaling cascades, leading to the upregulation of genes involved in cell motility and adhesion.
* **Extracellular Matrix Remodeling:** Matrix metalloproteinases (MMPs) are enzymes that degrade the extracellular matrix (ECM), creating pathways for LECs to migrate through. MMPs are activated by growth factors and cytokines, facilitating LEC movement.

**2. Cell Polarization and Adhesion:**
* **Directional Protrusion:** Once activated, LECs undergo polarization, forming a leading edge with specialized structures called lamellipodia and filopodia. These structures extend outward, sensing the ECM and guiding the cell in the direction of migration.
* **Adhesion and Detachment:** Integrins, transmembrane receptors that bind to ECM components, play a crucial role in cell adhesion. LECs express specific integrins that mediate their attachment to the ECM. As the LEC moves, integrins at the rear of the cell detach from the ECM, while new integrins at the leading edge attach, facilitating forward movement.

**3. Intracellular Signaling and Actin Dynamics:**
* **Rho GTPases:** Small GTPases, such as Rho, Rac, and Cdc42, are key regulators of cytoskeletal organization and cell migration. They activate downstream signaling pathways that regulate the assembly and disassembly of the actin cytoskeleton, which provides the force for cell movement.
* **Microtubules:** Microtubules play a role in maintaining cell shape and transporting organelles towards the leading edge of the migrating cell.

**4. Vessel Formation and Integration:**
* **Tip Cell Formation:** During lymphatic vessel development, LECs at the leading edge of the migrating vessel form tip cells. Tip cells are highly migratory and secrete signals that attract other LECs, forming new lymphatic vessels.
* **Branching and Fusion:** As LECs migrate and proliferate, they form branches that eventually fuse with existing lymphatic vessels, creating a complex network.

**5. Regulation and Control:**
* **Growth Factors and Cytokines:** The levels of growth factors and cytokines are tightly regulated to ensure that LEC migration occurs only when and where it is needed.
* **ECM Composition:** The composition of the ECM influences LEC migration by providing guidance cues and regulating cell adhesion.
* **Cell-Cell Interactions:** LECs interact with each other and with other cell types, such as pericytes and smooth muscle cells, to coordinate their migration and ensure proper vessel formation.

**6. Pathological Significance:**
* **Lymphangiogenesis:** Lymphatic endothelial cell migration plays a critical role in lymphangiogenesis, the formation of new lymphatic vessels. This process is essential for maintaining fluid balance, immune surveillance, and tissue repair.
* **Lymphatic Malformations:** Dysregulation of LEC migration can lead to lymphatic malformations, which are congenital abnormalities of the lymphatic system.
* **Cancer Metastasis:** LECs can contribute to the spread of cancer cells, as migrating LECs may transport cancer cells through the lymphatic system to distant sites.

**Conclusion:** Lymphatic endothelial cell migration is a complex and highly regulated process that is crucial for the development, maintenance, and function of the lymphatic vasculature. It is a dynamic process involving a coordinated interplay of growth factors, cytokines, extracellular matrix components, intracellular signaling pathways, and cytoskeletal reorganization.'
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Proteins (2)

Compounds (11)