MD NewslineThe Role of Interleukin-1ß in Breast Cancer Bone Metastasis

IL-1B’s multifaceted role in breast cancer bone metastasis emphasizes its potential as a therapeutic target, linking chronic inflammation to metastatic progression and the vicious cycle of bone resorption.

Interleukin-1B (IL-1B), a potent pro-inflammatory cytokine, plays a critical role in breast cancer progression and metastasis, particularly in bone. This comprehensive review examines IL-1B’s involvement in tumor growth, epithelial-to-mesenchymal transition (EMT), and the establishment of metastatic niches in bone. It also explores the cytokine’s influence on the vicious cycle of bone metastasis and evaluates preclinical studies on IL-1B inhibition as a therapeutic strategy. Combining anti-IL-1 therapies with standard treatments shows promise, though the complexity of IL-1B’s effects on primary and metastatic tumors necessitates further investigation.

Key Points:

• IL-1B’s Role in Tumor Progression:
  • IL-1B promotes EMT, facilitating tumor cell migration and invasion.
  • It regulates inflammation within the tumor microenvironment, aiding tumor growth.
  • IL-1B enhances angiogenesis, supporting tumor expansion and dissemination.
• Bone Metastatic Niche Formation:
  • IL-1B upregulates in the bone microenvironment upon the arrival of breast cancer cells.
  • It promotes the creation of a conducive niche for metastatic cells.
  • IL-1B stimulates the activity of osteoblasts and endothelial cells, expanding the metastatic niche.
• Vicious Cycle of Bone Metastasis:
  • IL-1B is pivotal in the vicious cycle of bone metastasis, enhancing osteoclast activity and bone resorption.
  • It triggers the release of growth factors from the bone matrix, fueling further tumor growth.
  • IL-1B’s role in osteoclast differentiation leads to excessive bone destruction.
• Therapeutic Implications:
  • Inhibition of IL-1B signaling reduces bone metastasis in preclinical models.
  • Anti-IL-1 therapies, such as Anakinra, show potential in combination with chemotherapy and immunotherapy.
  • Effective targeting of IL-1B may require consistent suppression to prevent dormant cell reactivation and metastatic outgrowth.
• Molecular Mechanisms:
  • IL-1B activation involves cleavage by Caspase-1, initiating a cascade that activates NF-κB, STAT3, and other signaling pathways.
  • IL-1B synergizes with TGFβ, promoting pro-tumorigenic environments through IL-17 and IL-22 secretion.
  • It enhances breast cancer cell aggressiveness via upregulation of IL-6 and IL-8.
• Preclinical Study Findings:
  • Genetic overexpression of IL-1B in breast cancer cells induces EMT and increases migratory and invasive capabilities.
  • IL-1B facilitates tumor cell extravasation and homing to the bone marrow.
  • Pharmacological inhibition of IL-1 signaling shows reduced metastatic outgrowth in mouse models.

Breast cancer (BC) is mainly diagnosed in early stages (90–95%), however 20–30% of these patients become metastatic and to this day incurable. Bone is the single most frequent site for metastases and is involved in about 70% of all metastatic patients. (Ecancermedicalscience)

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