Authors:
Danfeng Lin, Lesang Shen, Meng Luo, Kun Zhang, Jinfan Li, Qi Yang, Fangfang Zhu, Dan Zhou, Shu Zheng, Yiding Chen, Jiaojiao Zhou
The Value Of Understanding Circulating Tumor Cells
Cancer metastasis is a complex multistep process involving cancer cell invasion in the primary site, intravasation into circulation, survival in the circulation, extravasation from the circulation, and attachment to and colonization of the metastatic site. Circulating Tumor Cells are defined as tumor cells that have been sloughed from the primary tumor and are swept away by the circulatory or lymphatic systems. To date, most CTC research has focused on CTCs in the blood circulation. CTCs were first described in 1869 by Ashworth who observed “some cells” in the blood of a metastatic cancer patient with an appearance similar to tumor cells in the primary tumors. CTCs have been assumed to be the substrate of metastasis.
Although CTCs originate from the primary tumor, they are distinct from primary tumor cells, with EMT transition properties that help them break free from the primary tumor and facilitate intravasation into the bloodstream, dissemination in clusters of CTCs to increase metastatic potential, and exhibit stemness features that enhance their ability to initiate metastasis. However, most CTCs perish in the circulation, and only limited CTCs survive and infiltrate distant organs. Interactions between CTCs and the blood environment, including how CTCs escape immune surveillance in the blood, have been widely implicated in the metastatic mechanisms of CTCs.
It has taken more than a century for researchers to recognize the critical role of CTCs in cancer metastasis, due to the unique technical challenges required to isolate these very rare CTCs from the massive pool of circulating blood cells. However, in the past two decades, emerging technologies for CTC isolation have allowed research on the biology of CTCs and have facilitated the clinical applications of CTCs in cancer screening, treatment response monitoring, and prognosis evaluation.
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