Working with mice genetically engineered to develop human skin cancers, the team discovered that the protein plays a key role promoting — or inhibiting — metastasis, the spread of cancer from one area or organ to another.
Dubbed MIDKINE, the protein is secreted by melanomas — the most serious type of skin cancer — before travelling to a different part of the mouse body to kickstart cancer formation, they said.
In subsequent observations in humans, high levels of MIDKINE in the lymph nodes of skin cancer patients were predictive of “significantly worse” outcomes, the team reported in the science journal Nature.
This was the case even if there were no tumour cells in the lymph nodes.
“In MIDKINE we have found a possible strategy that merits consideration for drug development,” said Marisol Soengas of the Spanish National Cancer Research Centre in Madrid, a co-author of the study.
Early detection is important in melanoma. After it starts spreading, patient prognosis is usually poor.
It was long thought that melanoma prepares the organs it intends to colonise by activating the growth of fluid-transporting lymph vessels — first in and around the primary tumour, then the surrounding lymph nodes, and so on.
However, removing lymph nodes next to a melanoma tumour does not prevent metastases, meaning there is “something missing” in our understanding of the spread mechanism, said the researchers.
The new study offers a possible answer.
“When these tumours are aggressive, they act at a distance much earlier than previously thought,” said the authors.
MIDKINE travelled directly to the new cancer site irrespective of lymph vessel formation around the original tumour.
When MIDKINE was inhibited in mouse tumours, metastasis was blocked as well, said the team.
“These results indicate a change of paradigm in the study of melanoma metastasis,” according to Soengas.
The team used special mice to track metastasis through a luminescent protein that lights up when a new area of the body is affected by cancer formation.
What is not known is whether MIDKINE is transported in the blood, in lymph, or both.
In a comment, also published by Nature, Ayuko Hoshino and David Lyden of the Weill Cornell Medicine, a university in New York, said the study provided “much-needed insights” for the prediction of metastatic risk.
The work, they concluded, “might open a door to diagnostic and therapeutic strategies that aim to deal with metastases before they have a chance to arise.”
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