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Human Protein Engineered to Capture Circulating Tumor Cells

저자:   업로드:2017-07-03  조회수:

    Cancerous tumors are formidable enemies, recruiting blood vessels to aid their voracious growth, damaging nearby tissues, and deploying numerous strategies to evade the body’s defense systems.  But even more malicious are the circulating tumor cells (CTCs) that tumors release, which travel stealthily through the bloodstream and take up residence in other parts of the body, a process known as metastasis.


    While dangerous, their presence is also a valuable indicator of the stage of a patient’s disease, making CTCs an attractive new approach to cancer diagnostics. Unfortunately, finding the relative handful of CTCs among the trillions of healthy blood cells in the human body is like playing the ultimate game of needle-in-a-haystack: CTCs can make up as few as one in ten thousand of the cells in the blood of a cancer patient. This is made even more difficult by the lack of broad-spectrum CTC capture agents, as the most commonly used antibodies fail to recognize many types of cancer cells.




    Scientists at the Wyss Institute at Harvard University have engineered the human blood opsonin protein known as FcMBL, or Fc-mannose binding lectin, which was originally developed as a broad-spectrum pathogen capture agent, to target CTCs instead. The team reportedly used magnetic beads coated with FcMBL to capture 90% of seven different types of cancer cells.


    The novel approach could become useful in cancer diagnostics, according to the investigators.


    “The FcMBL capture technology may therefore provide a new tool for harvesting a broad range of CTCs with high efficiency as it targets tumor cell specific surface markers that are expressed across diverse cell types and retained throughout the metastatic process,” write the researchers in a paper (“An Engineered Human Fc-Mannose-Binding-Lectin Captures Circulating Tumor Cells”) that appears in Advanced Biosystems.


    "We were able to rapidly isolate CTCs both in vitro and from blood, including some that are not bound by today's standard CTC-targeting technologies," says Michael Super, Ph.D., lead senior staff scientist at the Wyss Institute and co-author of the research paper.


    Current CTC diagnostic systems frequently make use of a cancer cell marker, the epithelial cell adhesion molecule (EpCAM), which is highly expressed on the surface of tumor cells. However, EpCAM expression on cancer cells decreases when tumor cells transform into CTCs, ironically making EpCAM-based tests less useful precisely when it is most crucial to know that a patient's

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