How do cancer cells become more aggressive?

About 2 billion years ago, when multicellular organisms appeared, cancer Also appeared. Like a cancer evolutionist Athena Aktipis In “Cunning Cell”, “Cancer is not the enemy we call it in the usual sense. It is not an orderly and uniform army, united to kill us and be quick. On the contrary, it is just A group of disorganized, undisciplined, different cells , Will make a variety of responses to treatment.” In many cases, The most deadly risk of cancer is often not from the primary tumor, but from the spread of cancer .Some malignant tumor cells will break away from the original site, reach other tissues and organs of the body through various means, and then continue to grow to form new tumors. This process is called Transfer . Metastasis is not uncommon in cancer patients, but it is currently one of the least understood aspects of cancer biology. In a new study, a group of scientists tracked the development of metastatic cells through a new technology, which gave us a big step in our understanding of this process. They found a pattern of “aggressive spectrum” in the cells. Some cells are more likely to “keep in place” at the site of the primary tumor, while others are more likely to reach new parts of the body and invade other tissues or tissues. organ. Research indicates, It’s not just genetic mutations that promote the spread of cancer , The results of single-cell RNA analysis emphasized Gene expression patterns, that is, which genes the cell turns on or off, also play a key role in disease outcomes . The research has been published in Cancer Cells recently. Although scientists have described hundreds of gene mutations that are associated with normal cells becoming cancerous, their knowledge of the mutations that can cause cancer cells to metastasize is very limited. Some people believe that one possibility is that the process of metastasis also depends on other factors besides mutation, or that it is the result of too many abnormal combinations, so it is difficult to determine its characteristics. In order to better understand the biological changes that accompany the transfer, in the new study, the team plans to pass “evolution Bar code “(Its more professional name is CRISPR lineage tracking ) Technology to track this process in detail. Researchers have developed a new method that uses CRISPR/Cas9 To mutagenize the introduced synthetic DNA sequences, they are like barcodes “sticked” on cells. Subsequently, these modified cancer cells were injected into the pancreas of two experimental mice, allowing them to metastasize in the body. When cancer develops and spreads in the host mouse, the cell barcode is randomly “edited” by CRISPR/Cas9. The resulting editing model can be used to reconstruct the phylogenetic tree of cancer cells spreading and metastasis throughout the body. . This technology can help them observe new information that was previously unavailable.They combine this new technology with Single cell RNA sequencing Combine, rank cells according to their degree of metastasis, and then link these behavioral differences with changes in gene expression. Schematic overview of the new research. | Image source: K. Simeonov /Cancer Cell (2021) By observing about 28,000 cancer cells in multiple organs of the two experimental mice, the researchers were able to see which genes each cell turned on when the cancer cells spread from the pancreas to other organs and tissues. They also tracked the spread of cells in the body to determine whether certain cell lineages, that is, the same “cell family”, are more likely to metastasize than other lineages. In other words, for all these cells, scientists now know where they are in the body, and they also have a measure of their metastasis. At the same time, they also have information about the transcriptome of the cell, or it can be understood as the RNA of the cell. Molecular catalog. When the team checked the data together, they were surprised to find that about half of the clones (which can be understood as Different cancer cell groups ) Is limited to the scope of the primary tumor.And when they looked at the cell clones that had spread, they found There is only one distinctly dominant clone per mouse . This is very different from what scientists originally expected. The study found that a kind of clone (large circle in the picture) has a clear advantage in metastatic cells through lineage reconstruction. The different colors in the picture represent the location of the cells. | Image credit: Kamen Simeonov / UPenn The transcriptome profile of this dominant clone is different from other diffuse clones and clones confined to the primary tumor. The gene expression data of this most aggressive clone shows that It started with Epithelial-mesenchymal transition (EMT) Related genes , And this process of EMT is thought to give cancer some aggressive characteristics. Throughout the cloning, the research team found that if the EMT state of the cell is mapped into a continuous spectrum, from expressing many epithelial genes to expressing many mesenchymal genes, then Cells occupy different positions in this spectrum . The team noticed that many genes related to human cancer appeared in the genetic map of more aggressive cells, some of which have been predicted to be related to reduced survival rates. They also found that in a particularly aggressive clone in the second mouse, a gene family related to cancer characteristics appeared compared to other clones. Significant overexpression . The expression of this gene family may enhance the ability of metastasis in some way. In future work, the team hopes to further study the metastasis process and also explore new ways to apply this lineage tracking tool, such as studying developmental processes, stem cell biology, or the regeneration of some tissues and organs. They hope that this new method can better lead people to explore and even answer questions that could not be solved before. # Reative Team: Text: M ka # Reference source: https://penntoday.upenn.edu/news/pinpointing-how-cancer-cells-turn-aggressive https://www.sciencedirect.com/science/article/abs/pii/S1535610821002713?via%3Dihub [美] Athena Aktipis, “The Cunning Cell”, CITIC Publishing, Nautilus, June 2021 #Image Source : Cover source: Kamen Simeonov / UPenn