Identified: Signalling cascade involved in melanoma amoeboid cell aggression
Researchers have found new insight into the mechanisms by which a highly invasive subset of melanoma cells on the periphery of tumours—rounded amoeboid cells—contribute to tumour spread and metastasis.
In a paper published in Nature Communications (Oct. 20, 2020), the researchers report that the rounded-amoeboid cells demonstrated high Myosin II activity, high levels of the protein ki-67—associated with aggressiveness in cutaneous melanoma—and high tumour-initiating abilities. These traits all aid these cells at efficiently disseminating through the body and successfully forming new tumours, the authors write.
“An important observation of our study was that aggressive melanoma cells were not only very invasive but were good at dividing,” said lead author Irene Rodriguez-Hernandez, PhD, in a press release. “Therefore, such melanoma cells were capable of growing new tumours both in the skin and at a distant site such as the lung. Our work sheds some light on the ability of melanomas to form metastases very early in the progression of the disease.”
Dr. Rodriguez-Hernandez is a postdoctoral researcher at the Barts Cancer Institute, Queen Mary University of London, U.K.
In the study, the investigators studied melanoma cell lines and preclinical models and found that melanoma cells can initiate tumours at new sites via a signalling cascade that is also involved in embryonic development.
In the press release, the researchers note that melanocytes form from neural crest cells, which are highly migratory in the body during development, where the neural crest cells give rise to many different cell types.
“The molecules that melanoma cells use to become invasive and to grow are important for neural crest functions during human development,” said senior author Victoria Sanz-Moreno, PhD, in the release. “We have uncovered a mechanism by which cancer cells hijack this developmental program to become aggressive. It is a bit like melanoma has a ‘cellular memory’ to revert to that neural crest state.”
Dr. Sanz-Moreno is Professor of Cancer Cell Biology at the Barts Cancer Institute.
When the research team analyzed samples from primary tumours in melanoma patients, in an effort to see if the laboratory findings were representative of melanoma in clinic, they found that the edges of the patients’ melanoma tumours were enriched with rounded-amoeboid cells that expressed the signalling molecules that promote both growth and invasion.
The investigators say their findings emphasize the need to ensure these cells are removed during surgery by leaving a wide surgical margin after tumour excision. They also suggest they have identified potential new therapeutic targets for the development of medications to inhibit cancer cell dissemination and the formation of new tumours.