CD44, CD47 and MET Have been Found Related to Initiation of Metastatic Cancer Cells
Circulating tumor cells (CTCs) are now treated as a biomarker for prognosis and people think the CTCs are connected to cancer metastasis. But there is no clear clue to clarify how CTCs affect patients.
Some scientists thought only few CTCs will form secondary tumor in different organs as the metastasis process is very complex. They concluded the reason to be the characteristics of cancer stem cells as they hypothesized.
They developed a transplantation test for experimental detection of metastasis-initiating cells. They isolated circulating tumor cells from the blood of 350 breast cancer patients and transplanted them into the bone marrow of mice with defective immune systems. After more than one hundred transplantations, metastases actually started forming in the bones, lungs and livers of some of the animals. The result showed that CTCs indeed contain metastasis stem cells. But what characterizes these cells?
To clarify the molecular properties, researchers analyzed the surface molecules of those CTCs where the cell transplantation had led to metastases. In a systematic screening process, the research first isolated cells carrying a typical protein of breast cancer stem cells, which is CD44 that helps the cell settle in bone marrow. Then they screened this cell population for specific surface markers which help the cells to survive in foreign tissue, which include CD47 that protects from attacks by the immune system and a surface receptor that enhances the cells' migrato and MET that enhances the cells' migratory and invasive capabilities.
Further the study, they used a cell sorter which revealed all the characteristics of the three factors at once.
Researchers are glad to find that CD44, CD47 and MET that characterize metastasis initiating cells. Based on this, scientists could develop countermeasures, such as MET receptor inhibitor, CD44 antibody, or the therapeutic CD47 antibody etc. Actually the therapeutic antibodies targeting CD47 to inhibit its functions are already being developed and a substance inhibiting the activity of the MET receptor has already been approved and shows good effectiveness for treating a certain type of lung cancer.
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