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Tumors arise from a small population of cancer stem cells (CSCs) or tumor-instating cells. Cancer cells can rapidly reshape, destroy, or integrate into existing blood vessels. Tumor angiogenesis and blood vessels create a blood supply to the cancer tumor, also causing the spread, or metastasize, to new tissues through the blood.
Tumors produce protein factors that stimulate the formation of blood vessels to provide them with the food and oxygen they need. The process of blood vessel formation is called tumor angiogenesis. This is not to be confused with angiogenesis, the growth of blood vessels from the existing vasculature, which is part of the healing process.
A piece of an existing tumor would take over an adjacent blood vessel wall, putting cancer cells in direct contact with the circulation, and cancer cells could do so in a matter of hours. They didn’t have to invade past the blood vessels; they became the blood vessels and could release cancer cells into the blood flow.
Tumor vessels are more permeable than normal blood vessels. Their immature nature means they are poorly constructed with smooth muscle cells and may have a discontinuous endothelial cell lining with an abnormal basement membrane that makes them weak and vulnerable to the leaking of cancer stem cells.
Without a blood supply, tumor cells cannot spread or metastasize to new tissues. Tumor cells can cross through the walls of the capillary blood vessel at a rate of about one million cells per day. However, not all cells in a tumor are angiogenic. Angiogenic and nonangiogenic cells in cancer cross into blood vessels and spread; however, nonangiogenic cells give rise to dormant tumors when they grow in other locations. In contrast, the angiogenic cells quickly establish themselves in new places by developing and producing new blood vessels, resulting in the rapid growth of the tumor.
Trying to determine how groups of cells migrate to other parts of the body, the scientists used tissue engineering to construct a functional 3D blood vessel and grew breast cancer cells nearby. They observed the cancer cells reaching the blood vessel and taking over a patch of the cell wall. As a result of this attachment to the blood vessel, a cluster of tumor cells was quickly released into the bloodstream to travel to distant sites. Cancer cells also could constrict blood vessels, causing them to leak or pull on them.
Tumors with Slow or No Blood Flow
To ensure this result wasn't an artifact of the surgical procedure (e.g., trauma from the surgery), the researchers directly visualized the tumors through the thin skin of three patients and examined their tumor blood flow. They found, again, that approximately 50 percent of the blood vessels had no blood flow.
That’s a clinically significant finding, explained Dr. Skitzki, because “whether we’re talking about chemotherapy or immunotherapy, half of the inlets to the tumors are closed, so the therapies can’t get to different parts of the tumor.” High-Magnification Microscopy Visualizes Tumor Blood Vessels in Real-Time
An increasing body of evidence, initially from histopathological studies and subsequently from animal models and clinical trials, has uncovered an added layer of complexity: the possibility that some primary and metastatic tumors can develop and progress without angiogenesis by exploiting the pre-existing vasculature.
Hypoxia is a common feature of solid tumors. It develops because of the rapid growth of the cancer that outstrips the oxygen supply and impaired blood flow due to the formation of abnormal blood vessels supplying the tumor. Reports indicate that tumor hypoxia can activate angiogenesis, enhancing invasiveness and the risk of metastasis, boosting cancer survival, and suppressing anti-tumor immunity while impeding the therapeutic response. The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment.
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