Researchers reveal new mechanism behind skin cancer metastasis

Researchers from SciLifeLab, KTH and Stanford University, have identified a new type of cancer cells, responsible for the metastasis of skin cancer. The discovery might help researchers understand the metastasis of other types of cancers as well, and might lead to the investigation of new drug targets.

The new type of cancer cells are located at the outer parts of the tumor, adjacent to the surrounding tissue. These cells only make up a small part of each tumor but are highly mobile and communicate with both cancer and normal cells.

“These relatively few tumor cells are thus the cause of the tumor spreading and escaping the body’s immune system,” says co-first author Kim Thrane (SciLifeLab/KTH), in a press release from KTH.

In the study, published in the scientific journal Cell, the researchers investigated squamous cell cancer, a form of skin cancer that has a lot in common with other epithelial cell cancers in the skin, mucosa and glands.

“These forms of cancer make up almost 90 percent of all cancer cases. We therefore believe that the results of this study can increase the understanding of how many cancers grow and spread”, says Kim Thrane.

The researchers have analyzed tumor samples and normal skin tissue samples from 10 patients. In this way, they have been able to identify the differences that arise in a tumor, apart from what is happening in the cancer cells themselves.

“In the tumors we found several subpopulations of cancer cells that had a healthy counterpart in normal skin”, explains Kim Thrane.

The researchers also discovered a specialized type of cell different from every other cell in normal tissue. These cells, called tumor-specific keratinocytes (TSK), have the ability to invade the surrounding tissue. In addition, they have the ability to recruit cell types that increase the tumor growth rate, facilitating their spread to other parts of the body.

“We let human tumors from squamous cell cancer grow in mice. When we knocked out the genes that the TSK’s use to communicate with other cells, the tumor growth was inhibited”, says Kim Thrane.

Creating drugs that can inhibit this signaling pathway could potentially be used to effectively treat squamous cell cancer.

“Since squamous cell cancer is similar to many other types of cancers, we believe that our findings can increase the understanding of these cancers as well, leading to the investigation of new drug targets”, says Kim Thrane.

“The study also points to the realization that we can identify and localise tumor cells that appear to be more ’aggressive’”, explains Joakim Lundeberg (SciLifeLab/KTH).

Single-cell RNA sequencing and Spatial transcriptomic, a technique developed by SciLifeLab, KI and KTH, was used to spatially analyze the gene activity in the tissue.

“The combination of these two methods helped us solve the puzzle of what cell types are in the tumor, what they do, where they are, and which cells they communicate with, says Kim Thrane.


Last updated: 2020-07-10

Content Responsible: Johan Inganni(