Metastasis Markers

Marchetti and his team created a process to isolate circulating tumor cells from people with melanoma. They chose people who represented a range of stages, from primary to metastatic melanoma. 

They then injected these circulating tumor cells into mice and watched for melanoma tumors in the brain using MRI scans. Interestingly, these mice had brain tumor patterns that matched the human patterns of melanoma that spreads to the brain.  

“These patterns of brain metastasis – cerebellum, frontal lobe, temporal lobe – recapitulated results for clinical melanoma,” Marchetti says. And that means that predicting metastasis in mice can be translated into predicting metastasis in people, he says.

So Marchetti and his team took circulating tumor cells from these mice and compared them to circulating tumor cells taken from the people with melanoma. They looked at the cells’ genomic signatures – their DNA and the messenger RNA that cells use to make proteins.

They found the same common genomic signature in the circulating tumor cells taken from the mice and from the people with melanoma brain metastases. And they found this signature in the circulating tumor cells that were injected in the mice, as well as in cells isolated from a person with melanoma brain metastasis who was undergoing treatment. 

That genomic signature included several genes that are involved in regulating ribosomes, the cellular structures called organelles that assemble proteins. 

The genomic signature did not match that of circulating tumor cells taken from the people whose melanoma had not metastasized. This means that the circulating melanoma tumor cells that led to brain metastasis in mice and in humans are different from those circulating tumor cells that don’t cause metastasis. 

“This finding is relevant”, Marchetti says, “because we find it in several conditions, regardless of person or of mouse. It’s potentially huge and needs to be confirmed in larger numbers of people.” 

Although these results are exciting, Marchetti stresses that much more work needs to be done to confirm them and to develop blood tests or treatments for metastasizing melanoma. 

As a bonus, he says the process that he and his team developed is not limited to melanoma or to brain metastases. It could be used for other types of cancer and for metastases to other organs.

Not wasting any time, Marchetti and his team have already started on that further work.

About Dario Marchetti, PhD

Dario Marchetti, PhD, holds a doctorate from the University of Pavia, Italy, and completed postdoctoral fellowships at University of Illinois-Chicago, MD Anderson Cancer Center and Baylor College of Medicine in Houston, holding faculty appointments there. In 2019, he joined UNM, where he is a tenured Professor in the Departments of Internal Medicine and Pathology. Dr. Marchetti is a recognized expert and international authority in the biology and clinical utilities of Circulating Tumor Cells (CTCs) directly isolated from blood of cancer patients.

Paper Reference

"The RPL/RPS gene signature of melanoma CTCs associates with brain metastasis" was published online on November 2, 2022, in Cancer Research Communications. (https://aacrjournals.org/cancerrescommun). Authors are: Tetiana Y. Bowley, Irina V. Lagutina, Carol Francis, Sinduja Sivakumar, Reed G Selwyn, Erik Taylor, Yan Guo, Bridget N. Fahy, Bernard Tawfik, and Dario Marchetti.