Joan Massagué and the Origin of Cancer Metastasis

Joan Massagué leads a research group at the Sloan Kettering Institute and recently discovered the mechanism of cancer metastasis. This breakthrough could change the way doctors treat this disease.
Joan Massagué and the Origin of Cancer Metastasis

Last update: 15 April, 2021

Joan Massagué may be remembered as the man who discovered the origin of cancer metastasis. A phenomenal scientific breakthrough that finally explains the way in which atypical cancer cells settle in other organs.

The scientist leads a research group at the Sloan Kettering Institute in New York City. There they’ve been investigating questions related to neoplasms for a long time, and so this discovery is part of a long journey.

Basically, the paradigm changed after being able to explain that tumor cells replicate the way the body heals wounds in order to generate metastasis. This article will explain how medicine had a different concept on this subject.

This advance is important because nine out of ten cancer patients die as a result of metastasis. This is why the publication of this research in the Nature cancer journal is confirmation that there’s hope for reducing this mortality.

As you’ll see below, the central axis of the discovery is the ability of tumors to manufacture the L1CAM molecule. It’s the same substance that damaged tissues in the body make to heal wounds. Hence the surprise.

What’s cancer metastasis?

Let’s first review what metastasis is, in order to understand Joan Massagué’s discovery.

Metastases are the appearance of a primary tumor in an organ or tissue other than the one that first gave rise to it. The cells migrate from the original location of cancer to settle in another place and nest.

This seems logical and expected in the evolution of cancer, although research on the subject agrees it isn’t so easy for a neoplasm to cause metastasis.

A metastatic cell must be able to separate from the primary tumor, travel through the body, and find a place to settle properly. There’s no metastasis if any one of these steps fails.

Different cancers have specific sites where they tend to metastasize. Breast cancer, for example, usually spreads to the bones and lungs. Prostate cancer also gives rise to secondary bone tumors.

Lung cancers and colon cancer usually nest in the liver. In any case, any tissue can become the recipient of a neoplasm.

Various cells metastasizing.
Bone metastases are a common development in breast and prostate cancer.

Previously beliefs about cancer metastasis

Joan Massagué’s discovery about the origin of metastases shatters previous beliefs in the field of medicine. It’s a complete turnaround in scientific knowledge in a way.

Traditionally, we assumed that cancer had a genetic component of mutation that resulted in metastasis. Tumor cells would migrate because of their ability to mutate and thus link to other tissue.

People have been questioning this traditional knowledge since the 1980s, although it persisted as the accepted one. A researcher named Harold Dvorak spoke of metastases as injury processes that failed to heal properly. This is linked to the concept of the discovery by Joan Massagué and his team.

The origin of metastases is attributed to cell reprogramming, but not to mutation, in the new paradigm that this research signifies. This means that tumor cells don’t mutate but turn on or off genes they already possess in order to migrate and nest elsewhere.

Some cells homologize their behavior to the stem cells when reprogrammed. Thus, they generate affinity with a different tissue.

A lab technician looking inside the microscope.
Genetic mutations don’t give rise to metastasis, reprogramming does.

What Joan Massagué discovered

Joan and his team studied metastasis for years and already knew that only 1% of all neoplastic cells can migrate and metastasize before investigating the origin of this process.

This low prevalence led them to ask why so few cells were able to do so and their research pointed in that direction. So they looked at the molecule L1CAM, which they knew finds an expression in metastatic cells.

L1CAM doesn’t occur within healthy body tissues, only in damaged epithelial cells. The human body uses it to repair wounds by bringing the cells together.

Metastases express L1CAM to gain adherence, simulating the wound repair process that normally happens. Therefore, the research team defined the mechanism of metastasis as the repair of a wound that’s not a wound, in a place that doesn’t have one.

A second study by the group led by Joan Massagué, also published in Nature, confirms that metastasis is due to reprogramming. Metastatic cells produce other molecules identical to those used by the body to fill wounds and form scars in addition to L1CAM.

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