Research results may help identify new targets for inhibiting the spread of melanoma

Review by Emily Henderson, Bachelor of ScienceOctober 20, 2020

A study led by Queen Mary University of London reveals new insights into the mechanisms that melanoma cells employ to form tumors in secondary areas around the body. The results of this study may help control the spread of melanoma and identify new targets for guiding treatment decisions in the clinic.

Melanoma is an aggressive type of skin cancer, and melanoma cells easily spread throughout the body even in the early stages of the disease. The spread of cancer from one part of the body to another in a process called metastasis is a major cause of cancer death.

In order for cancer to metastasize, cancer cells must be separated from the primary tumor, travel through the bloodstream or lymphatic system, settle in new parts of the body, and grow into new tumors.

The results of this study are today Nature CommunicationsThere is a subset of highly invasive melanoma cells called “rounded amoebic” cells around the edge of the tumor that not only spread very efficiently throughout the body, but also form new tumors. Also revealed to be very successful.

An important observation of our study was that aggressive melanoma cells were not only highly invasive, but also superior in division. Therefore, such melanoma cells were able to grow new tumors both in the skin and in distant sites such as the lungs. Our research highlights the ability of melanoma to form metastases at a very early stage of disease progression. “

Dr. Irene Rodriguez Hernandez, lead author of research at Queen Mary University of London

New tumorigenesis initiated by a powerful signal set

Using melanoma cell lines and preclinical models, the team discovered that melanoma cells can initiate tumors at new sites via a strong signaling cascade. Melanoma cells produce a molecule called Wnt11, which binds to a second molecule on the surface of the cancer cell called FZD7.

Upon binding, these molecules activate a protein called DAAM1, which regulates a protein called RhoA. This is a master regulator of cancer infiltration. This series of events allows melanoma cells to invade surrounding tissues and grow new tumors when they reach new parts of the body.

Interestingly, these signaling molecules are also important during human development from the embryo. Melanoma is derived from pigment-producing cells in the skin called melanocytes. Melanocytes are formed from a series of cells called neural crest cells. Neural crest cells are highly mobile. They move to different areas of the body and produce many different cell types during human development.

Professor Victoria Sanz-Moreno of Queen Mary University of London, who led the study, said: “The molecules that melanoma cells use to infiltrate and grow are important for neural crest function during human development. Cancer cells have elucidated the mechanism. They hijack this developmental program and become aggressive. Black It is a bit like a tumor having “cell memory” to return to its neural crest state. “

To determine if their laboratory findings were representative of melanoma in the clinic, the team analyzed samples from primary tumors in patients with melanoma. Their analysis revealed that the edges of melanoma tumors were enriched with round amoebic cells expressing signaling molecules that promote both growth and infiltration.

The study was conducted in collaboration with researchers at the Francis Crick Institute and King’s College London and was funded by Cancer Research UK, Barts Charity, Fundacion Alfonso Martin Escudero, and Marie Sklodowska-Curie Actions.

Impact on melanoma treatment

Because metastatic cancer kills the majority of cancer patients, there is an urgent need for therapeutic intervention to prevent the spread of the cancer. The results of this study have important implications for surgical intervention.

Because the cells that initiate the spread of melanoma are located on the edge of the tumor, these dangerous cells can be removed during surgery by leaving a large surgical margin of cancer-free tissue when removing the tumor. It is important. The study also identifies a major player in metastatic melanoma that may be the target of drugs to block the dissemination of cancer cells and the formation of new tumors.

The team will continue to define a panel of markers to identify these highly dangerous amoebic infiltrating cancer cells and attempt to separate them from the blood to determine prognostic potential. In addition, they are working on other solid tumors to see if the observations spread to other types of cancer.