[2] One of the genes that contributes to intravasation codes for urokinase (uPA), a serine protease that is able to proteolytically degrade various extracellular matrix (ECM) components and the basement membrane around primary tumors.
[3] uPA also activates multiple growth factors and matrix metalloproteinases (MMPs) that further contribute to ECM degradation, thus enabling tumor cell invasion and intravasation.
[4][5] Studies have revealed that macrophages enhance tumor cell migration and intravasation by secreting chemotactic and chemokinetic factors, promoting angiogenesis, remodeling the ECM, and regulating the formation of collagen fibers.
[10] Some studies suggest that cancer cells actively move towards blood or lymphatic vessels in response to nutrient or chemokine gradients,[6] while others provide evidence for the hypothesis that metastasis in its early stages is more of a random behavior.
[10] The first step in this process is specific adhesion to venous endothelial cells, followed by adherence to proteins of the subendothelial basement membrane, such as laminin and types IV and V collagen.