Pro-resolving lipid mediators stimulate the resolution of breast cancer in experimental models
OA Version
Citation
Abstract
Although the re-emergence of tumor growth remains a leading contributor to breast cancer-related deaths, the primary mechanistic functions are insufficiently explained and poorly understood. Cytotoxic therapies aim to induce apoptosis of cancerous tissue to reduce tumor burden. However, the consequent tumor debris promoted by chemotherapy and anti-estrogen therapy triggers the growth of cancerous tissue by disrupting the resolution of inflammation and creating environments that support inflammation and tumor formation. Our investigation reveals that therapy-generated tumor debris prompts primary tumor growth when co-administered with nontumorigenic tumor cells, inciting a macrophage-mediated pro-inflammatory and pro-angiogenic response. This highlights the imperative role of tumor cell debris in invasive breast cancer. Subsequently, to assess the potential impact of enhancing debris clearance, we examined the effects of specialized pro-resolving lipid mediators, maresin 1, as well as maresin conjugates in tissue regeneration 1 and 2, in standard models of murine medullary breast adenocarcinoma (E0771) replicating estrogen receptor-positive breast cancer. At nanogram concentrations, these mediators significantly reduced tumor growth without toxicity, inhibiting angiogenesis and mitigating a therapy-induced cytokine storm. Moreover, specific specialized pro-resolving mediator receptors for resolvin D1, resolvin E1, and maresin 1 were expressed and localized in the immune and tumor microenvironment. Overall, this suggests that the maresins pathway constitutes a promising medicinal strategy for resolving inflammation in breast cancer.
Description
2024
License
Attribution-NonCommercial-NoDerivatives 4.0 International