Cancer, it is known, may establish itself and spread by means of deviant signaling, which includes the emission of signaling molecules by tumor cells. In the case of breast cancer, tumor cells may amplify their messaging rather like the snake oil salesmen of old, through shills, penetrating healthy tissue as though it were a community of easily deceived innocents.
According to researchers at Johns Hopkins, breast cancer cells release signaling molecules at a heightened level, influencing lymphatic endothelial cells, which respond by producing proteins called CCL5 and VEGF. CCL5 attracts tumor cells to the lungs and lymph nodes, and VEGF increases the number of blood vessels and makes them more porous, allowing tumor cells to metastasize and infiltrate the lungs.
And so the breast cancer cells not only amplify their suspect hawking, they act through intermediaries, recruits prepped to perpetrate an elaborate deception. Shills.
This finding was presented September 2 in Nature Communications, in an article entitled, “Breast cancer cells condition lymphatic endothelial cells within pre-metastatic niches to promote metastasis.”
“LECs within the lungs and lymph nodes, conditioned by tumor-secreted factors, express CCL5 that is not expressed either in normal LECs or in cancer cells, and direct tumor dissemination into these tissues,” wrote the authors. “Moreover, tumor-conditioned LECs promote angiogenesis in these organs, allowing tumor extravasation and colonization.”
The authors, led by Aleksander Popel, Ph.D., relied on animal and cell culture experiments to show that “lymphatic endothelial cells (LECs), a component of LVs within pre-metastatic niches, are conditioned by triple-negative breast cancer (TNBC) cells to accelerate metastasis.”
“It was surprising to find that LECs can play such an active and significant role in tumor spread,” Dr. Popel noted. “Conventionally, lymphatic vessels are regarded mainly as passive conduits through which tumor cells spread from the primary tumor and eventually metastasize. However, we now know that lymphatic vessels enable metastasis, and other studies also show that they play an important role in whether or not immune cells recognize and attack cancer cells.”
The study also demonstrated the antimetastatic activities of multiple repurposed drugs. For example, maraviroc, a drug already approved for treating HIV infection, blocked the CCL5 signaling and prevented metastasis. Additional experiments used a combination of maraviroc and a drug that blocks the VEGF protein. This combination, the researchers asserted, could be an effective way to prevent metastatic disease in human breast cancer patients.
Because the antiretroviral drug maraviroc has already been approved by the FDA and has been shown safe for long-term oral use, it could be tested in clinical trials sooner rather than later, remarked Dr. Popel.