T cells attacking cancer cells. 3D computer illustration of T lymphocyte white blood cells (white) destroying cancerous cells (blue/purple). T lymphocytes, or T cells, are a type of white blood cell and a component of the body's immune system. They recognise a specific site on the surface of a pathogen or foreign object (antigen), bind to it, and attract antibodies or cells to eliminate it.

 In a new study to identify individual cancer cell genes, researchers found an aggression in cells that emerged from the primary tumor and eventually became metastatic.

The group’s findings show that it is not just genetic mutations that can lead to the spread of cancer. Some genes are activated, while others are inactivated, playing a key role in the disease. While scientists have identified hundreds of genetic mutations that lead normal cells to become cancer, did not detect mutations that make cancer cells metastatic.

To trace the genealogy, the researchers developed a new method {using CRISPR} for mutagenesis and prepared cancer cells that were injected into mice and allowed to metastasize.

By looking at about 28,000 cancer cells in multiple organs of the two mice, the researchers were able to see which genes were activated in each cell as the cancer spread from the primary site. They also looked at which specific generations were more metastatic than others. When the research team was surprised to find that about half of the clones, or cancer cell populations, were confined to primary tumors and from the clones that had spread, they found only one dominant in each .

The transcriptional profile of the dominant clone in metastases as well as other clones that spread from the primary tumor, were different from each other and from clones confined to the primary tumors. Gene expression data from this aggressive clone revealed that it had activated genes associated with what is known as epithelial mesenchymal transition (EMT), a process that gives cancer some of its aggressive properties. The genetic profile of the most aggressive cells shows many correspondences with genes associated with human cancer.

Despite genetic potential, most cancer clones are not metastatic, but metastatic aggression peaks with cell transition to EMT. The researchers also found that in a highly aggressive clone, a family of genes associated with cell migration and the ability of blood vessels to enter and exit was dramatically overexpressed compared to other clones.

Finally, gene proliferation of the S100 family was observed in metastatic subpopulations.

SOURCE: University of Pennsylvania {Cancer Cell, June 2021}