In a new study, researchers found a lipid-regulating protein that conveys what the researchers describe as “superpowers” onto prostate cancer cells, causing them to aggressively spread.
In studies 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 research was conducted by Johns Hopkins Kimmel Cancer Center scientists.
In the human cell line experiments, when the researchers 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.
In every prostate cancer cell line tested, 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 researchers 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 twofold to fivefold 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 could potentially be used as a biomarker, alerting clinicians to a risk of metastasis.
Interventions are being studied but are challenging because all cells need lipids. Any treatments aimed at inhibiting lipids would have to specifically target cancer cells.
Ongoing studies are aimed at better understanding the inflammatory process and ways to stop its ability to fuel cancer spread.
For example, the researchers want to understand why the inflammation draws cells, called macrophages, that further exacerbate the inflammatory process but does not attract beneficial T cells that could attack cancer, and if lipid cells could be sending signals that affect immune checkpoints, which are the immune system on and off switches.
One author of the study is Marikki Laiho, M.D., Ph.D., the director of the Division of Molecular Radiation Sciences.
The study is published in the journal Molecular Cancer Research.
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