In a recent study from Johns Hopkins Kimmel Cancer Center, researchers found a lipid-regulating protein conveys what the researchers describe as “superpowers” onto prostate cancer cells, causing them to aggressively spread.
The researchers found in experiments of human prostate cancer cell and stromal cell lines, when the lipid-regulating protein, called CAVIN1, was removed from stromal cells—the connective tissue cells in and around tumors—the cells no longer used the lipids.
Instead, cancer cells feasted on lipids in the environment, using them as fuel, including to make hormones that feed cancer.
The study is published in the journal Molecular Cancer Research. One author is Marikki Laiho, M.D., Ph.D.
In the human cell line experiments, when the team took CAVIN1 away from stromal cells called fibroblasts, the stromal cells no longer used the lipids, but the lipids remained in the environment, and to the researchers’ surprise, they became a smorgasbord for the cancer cells.
They found tumor cells universally had an appetite for the lipids, using them to fuel growth, strengthen the protective membrane around the cell, synthesize proteins, and make testosterone to support cancer’s growth.
As a consequence, the tumor cells behaved more aggressively, exhibiting invasive and metastatic behavior.
The team says just having access to the lipids gave the tumor cells more power. The tumor is the same tumor, but the behavior of the tumor changes.
In addition, when the stromal fibroblasts did not use the lipids, they changed and started to secrete inflammatory molecules that altered the tumor microenvironment. Inflammation is a characteristic long known to promote cancer.
To confirm their findings, the team conducted similar experiments in mouse models.
Although the presence or loss of CAVIN1 did not impact the speed of tumor growth, lack of CAVIN1 caused cancer to spread.
All of the mice with tumors that did not express CAVIN1 had a strong increase in metastasis. The tumors also had a fortyfold to a hundredfold increase in lipids and inflammatory cells.
The researchers say the loss of CAVIN1 in tumor cells may be used as a biomarker, alerting doctors to a risk of metastasis.
Any treatments aim at inhibiting lipids would have to specifically target cancer cells.
The team’s future work aims to have a better understanding of the inflammatory process and ways to stop its ability to fuel cancer spread.
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