In the blood of patients with advanced or metastatic cancer, circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) are much higher than patients with early cancer. Using this feature, researchers want to develop them into biomarkers for the diagnosis of metastatic cancer. Researchers believe that if it is possible to isolate circulating tumor cells associated with different stages of the tumor, it may be possible to understand the key mechanisms of cancer progression and spread. These thoughts have spawned a "liquid biopsy." Now, researchers have learned that CTC, ctDNA and exosomes isolated from body fluid samples can not only indicate the severity of the tumor, but also the cell diversity that the tumor has at different stages. The development of high-sensitivity and high-specific detection methods will have great value in the diagnosis of cancer. Today, we will combine the special issue of Nature Biomedical Engineering to give readers an early diagnosis topic. In this article, we review the biological properties of CTC, ctDNA and exosomes, present their current diagnostic methods, and discuss potential clinical applications.
â–² Recently, Nature Biomedical Engineering launched the early diagnosis topic (Source: Nature Biomedical Engineering)
Circulating tumor cells
The primary lesion of cancer releases some tumor cells into the bloodstream. These cells are generally invasive and tolerant to anoikis. Therefore, they can settle in organs other than the primary site of the tumor (such as the liver, bones, lungs, and brain) to produce new tumors.
Although the current research on these cells is still very inadequate, the researchers believe that these cells may be dependent on the concentration gradient of chemokines or migrate depending on the specific receptors expressed on the surface of these cells. Some studies have shown that if these cells are to be detached from the primary lesion or other metastatic sites, they must first acquire an invasive trait that can help with migration, which is associated with epithelial-to-mesenchymal transition (epithelial-to-mesenchymal transition). EMT) related. The researchers even believe that tumor cells do not have to complete all the steps of EMT, enough to produce new tumors - this transformation makes tumor cells highly plastic and allows them to undergo mesenchymal-to-epithelial transition (mesenchymal-to-epithelial transition) , MET) has the potential to make them easy to root at other sites in the body. Currently, researchers are validating the role of the EMT/MET model in cancer patients.
â–² Epidermal-mesenchymal transition allows tumor cells to be highly malleable (Source: Wikipedia)
Some clinical studies have shown that the life cycle of CTC should be extremely short, probably only 1-2.4 hours. However, these cells will try their best to live longer. In some studies, CTCs that are susceptible to attack by immune cells disguise themselves by expressing PD-L1 on the cell surface, inactivating the immune system. In other studies, platelet-encapsulated CTCs also have better protection against immune system-mediated cell lysis. The researchers point out that, in fact, because tumor cells tend to accumulate and stay in the microvasculature, they are prone to extravasation and thus leave the blood circulation. It is this short “free rider†that plays a decisive role in the transfer of cancer.
Currently, the CTC enrichment methods often used by researchers make use of the physical or biological properties of these cells. For example, we can use antibodies to specifically bind to CTCs that express epithelial cell-adhesion molecules (EpCAM), or to distinguish between blood cells and large tumor cells. On the other hand, we can also use the "reverse enrichment" method to remove blood cells in the blood and leave tumor cells.
Regardless of the method used, these enriched cells will be used for immunological, cellular, and functional analyses. For example, in the past 10 years, researchers have used EPISPOT (epithelial immunospot) technology to detect CTCs in many different cancer types. In addition, long-term culture of CTC, or xenograft CTC in immunodeficient mice, can be used to detect the effects of drugs.
â–² Principles of EPISPOT technology (Source: Clinical Cancer Research)
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