A new study conducted at the VIB-KU Leuven Center for Cancer Biology in Belgium has labeled the protein Caveolin-1 as a high-potential pursuit in the fight against cancer. Many research projects have already implicated this protein in both tumor-promotive and suppressive functions, but its exact role remained elusive. By examining macrophages at the sites of metastases, the scientists have now described the ‘anti-metastatic surveillance’ role of Caveolin-1 for the first time.

The new paper, published in the journal Cell Reports, was conducted by a team led by Professor Massimiliano Mazzone (VIB-KU Leuven). His lab has been focusing on the tumor microenvironment for some time now, gradually disentangling topics, such as tumor oxygen shortage, angiogenesis, macrophages, and anti-cancer immunity. This fundamental groundwork has now been stimulated by a European ERC grant on metabolic immunoregulation in cancer and tumor immunotherapy.

The gatekeepers of our lungs

While the role of tumor-associated macrophages at each step of cancer progression is already well established, the biology of ‘metastasis-associated macrophages’, their counterparts at the sites of cancer metastases, has been almost neglected. Understanding this field, however, is of the utmost relevance, as metastases cause no less than 90% of human cancer deaths.

In this research, the team describes for the first time the mechanism of Caveolin-1 in metastatic macrophages. They saw that upregulation of this protein in the lung environment clearly hinders metastatic growth.

Professor Mazzone: “A surprising outcome, since macrophages are traditionally associated with cancer progression. But at the same time, the anti-metastatic, patrolling function of Caveolin-1 makes sense when one considers the relevance of the immune system in the lungs as the first barrier against (inhaled) pathogens and external bodies. You could say Caveolin-1 is a gatekeeper—high expression can protect the body against foreign bodies and diseases, while downregulation is pro-metastatic.”

Caveolin-1 as a gatekeeper

Previous studies already associated the loss of Caveolin-1 with more aggressive proliferation—and worse patient outcomes—in several types of cancer. Professor Mazzone’s findings directly confirm the suggestion that this protein may yield promising therapeutic perspectives.

Professor Mazzone: “We have now learned that there is a huge difference in immunity at the metastasis compared to the primary tumor. And since metastasis is what kills most cancer patients, this research avenue deserves much more attention, which describes perfectly the direction of our next research projects!”