Monday, February 14, 2022

Breast Cancer Cells Churn Out Cholesterol to Fuel Metastasis

Good news! Cancer is history!

"High levels of cholesterol in the blood, as a result of diet or disease, have been associated with an increased risk for breast cancer recurrence. Studies suggest that cancer cells may use this molecule to fuel tumor growth or to impair the immune system. But a study published this week (February 2) in Molecular Therapy reports that cholesterol synthesis can also take place within tumor cells themselves, stimulating metastatic growth. This process is mediated by communication between triple negative breast cancer (TNBC) cells and fibroblasts from the lungs. Researchers were able to inhibit this signaling cascade and reduce lung metastasis by treating mice with the most common cholesterol-lowering drugs—statins. ..."

From the abstract:
"Triple-negative breast cancer (TNBC) has a high propensity for organ-specific metastasis. However, the underlying mechanisms are not well understood. Here we show that the primary TNBC tumor-derived C-X-C motif chemokines 1/2/8 (CXCL1/2/8) stimulate lung-resident fibroblasts to produce the C-C motif chemokines 2/7 (CCL2/7), which, in turn, activate cholesterol synthesis in lung-colonizing TNBC cells and induce angiogenesis at lung metastatic sites. Inhibiting cholesterol synthesis in lung-colonizing breast tumor cells by pulmonary administration of simvastatin-carrying HER3-targeting nanoparticles reduces angiogenesis and growth of lung metastases in a syngeneic TNBC mouse model. Our findings reveal a novel, chemokine-regulated mechanism for the cholesterol synthesis pathway and a critical role of metastatic site-specific cholesterol synthesis in the pulmonary tropism of TNBC metastasis. The study has implications for the unresolved epidemiological observation that use of cholesterol-lowering drugs has no effect on breast cancer incidence but can unexpectedly reduce breast cancer mortality, suggesting interventions of cholesterol synthesis in lung metastases as an effective treatment to improve survival in individuals with TNBC."

Breast Cancer Cells Churn Out Cholesterol to Fuel Metastasis | The Scientist Magazine® A study uncovers a novel connection between the biomolecule and cancer progression




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