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Intravasation is the invasion of cancer cells through the basement membrane into a blood or lymphatic vessel. Intravasation is one of several carcinogenic events that initiate the escape of cancerous cells from their primary sites. Other mechanisms include invasion through basement membranes, extravasation, and colonization of distant metastatic sites. Cancer cell chemotaxis also relies on this migratory behavior to arrive at a secondary destination designated for cancer cell colonization.
A newly identified metastasis suppressor, p75 neurotrophin receptor (p75NTR), is able to suppress metastasis in part by causing specific proteases, such as uPA, to be downregulated.
Tumor-associated macrophages (TAMs) have been shown to be abundantly present in the microenvironments of metastasizing tumors. 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.
Groups of three cell types (a macrophage, an endothelial cell, and a tumor cell) collectively known as tumor microenvironment of metastasis (TMEM) can allow tumor cells to enter blood vessels.
In active intravasation, cancerous cells actively migrate toward and then into nearby blood vessels. 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. The final step is the adhesion of the metastatic tumor cell to connective tissue elements such as fibronectin, type I collagen, and hyaluronan, which is required for the movement of the tumor cell into the subendothelial stroma and subsequent growth at the secondary site of colonization.
Passive intravasation refers to a process in which tumors metastasize through passive shedding. Evidence for this is seen when the number of tumor cells released into the circulation increases when the primary tumor experiences trauma. Cells growing in restricted spaces have been shown to push against each other, causing blood and lymphatic vessels to flatten, potentially forcing cells into the vessels.
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