Break the original cognition and uncover the "silent killer" among cancer cells
Certain stem cells in a resting state will not only avoid tumor treatments that prevent cell proliferation and induce apoptosis, but also develop drug resistance through dormancy, and can mutate and reshape tumor epithelial cells that are transformed into a proliferating state. This leads to rapid tumor growth and recurrence.
Such stem cells are called "silent killers."
◎Our reporter Chen Xi, correspondent Wu Junhui
On February 18, the reporter learned from Nankai University that researchers from Nankai University, Southern Medical University, Tianjin Medical University, and Yale University in the United States published an article in the latest issue of the international authoritative academic journal Advanced Science. Research results.
They used the same single-cell transcriptome sequencing and telomere length analysis technology to discover the different states and molecular characteristics of colorectal cancer stem cells.
They found that certain stem cells in a resting state will not only avoid tumor treatments that prevent cell proliferation and induce apoptosis, but also develop drug resistance through dormancy, and can mutate and reshape tumors that transform into a proliferating state. Epithelial cells, leading to rapid tumor growth and recurrence.
Such stem cells are called "silent killers."
This discovery has changed the traditional cognition of cancer stem cells in the past, and provided new ideas for cancer treatment, especially the inhibition of tumor recurrence.
The initiator of tumor metastasis and recurrence
Colorectal cancer is the third most common malignant tumor disease, and its mortality rate is also ranked third in the world, and it is showing a trend of younger onset. Studies have shown that tumor metastasis and recurrence are the main causes of death for most patients with terminal colorectal cancer.
Further studies have shown that cancer stem cells are the potential culprit for the recurrence of colorectal cancer patients after treatment.
However, what are the true characteristics of cancer stem cells, their proportion in tumors, how they cause disease, why they develop drug resistance, and a series of key issues are still not clear enough.
To get rid of the limitation of thinking that the tumor was studied as a mixed whole in the past, to understand in situ tumor stem cells more clearly, in-depth and accurately has become the key to solving the problem.
To this end, the researchers used integrated single-cell technology to conduct an in-depth analysis of patients' primary colorectal cancer cells.
As a result, it was found that the proportion of truly strong stem cells is extremely rare.
Surprisingly, these cancer stem cells are usually in a resting state, have low telomerase activity, and because they do not proliferate, they can maintain a relatively short telomere length.
Research results show that these "silent" cancer stem cells can be remodeled into tumor epithelial cells with high proliferation activity, longer telomeres, and activation of genes related to telomere maintenance such as telomerase.
New discoveries will optimize tumor treatment strategies
Telomeres are cap-like structures that exist at the ends of eukaryotic chromosomes and maintain a stable genome. Most somatic cells have telomere lengths that are not maintained by telomerase and will continue to shorten as cells divide and eventually age.
However, it is known that more than 90% of tumor cells can rely on telomerase to maintain telomeres to achieve an immortal state.
Therefore, inhibiting telomerase activity has become a possible way to treat tumors.
"At present, it is generally believed that cancer stem cells have long telomeres and high telomerase activity. But our research has found that, in fact, cancer stem cells have different states." One of the corresponding authors of the paper, the School of Life Sciences, Nankai University, Said Professor Liu Lin from the Institute of Translational Medicine and the State Key Laboratory of Medicinal Chemical Biology, People's Hospital of Nankai University.
"We also found that tumor epithelial cells and resting tumor stem cells have common surface molecular markers, so the population that was previously considered tumor initiating cells or tumor stem cells may be tumor epithelial cells." Liu Lin said, Subsequent higher-throughput single-cell analysis results for the entire tumor tissue and adjacent tissues also confirmed the above findings.
The results of these studies indicate that tumor recurrence and metastasis are closely related to resting tumor stem cells.
Although traditional tumor therapy can kill tumor cells in a proliferating state, tumor stem cells in a resting state may develop drug resistance.
Similarly, telomerase inhibitor drugs can only act on proliferating telomerase-positive tumor cells, but cannot target tumor stem cells with short telomeres, low telomerase activity, and their resting state. effect.
These findings will provide a useful reference for optimizing tumor treatment strategies, combining targeting tumor stem cells and alleviating tumor drug resistance.