Xiaogen Tang’s research while affiliated with Jinan University and other places

Breast cancer is the leading cancer diagnosed in women globally, with brain metastasis emerging as a major cause of death, particularly in human epidermal growth factor receptor 2 positive and triple-negative breast cancer subtypes. Comprehensive understanding of the molecular foundations of central nervous system metastases is imperative for the evolution of efficacious treatment strategies. Lipocalin-2 (LCN2), a secreted iron transport protein with multiple functions, has been linked to the progression of breast cancer brain metastasis (BCBM). In primary tumors, LCN2 promotes the proliferation and angiogenesis of breast cancer cells, triggers the epithelial-mesenchymal transition, interacts with matrix metalloproteinase-9, thereby facilitating the reorganization of the extracellular matrix and enhancing cancer cell invasion and migration. In brain microenvironment, LCN2 undermines the blood-brain barrier and facilitates tumor seeding in the brain by modulating the behavior of key cellular components. In summary, this review meticulously examines the fuel role of LCN2 in BCBM cascade, and investigates the potential mechanisms involved. It highlights the potential of LCN2 as both a therapeutic target and biomarker, indicating that interventions targeting LCN2 may offer improved outcomes for patients afflicted with BCBM.

Background Meningioma is the most common primary intracranial tumor with a high frequency of postoperative recurrence, yet the biology of the meningioma malignancy process is still obscure. Methods To identify potential therapeutic targets and tumor suppressors, we performed single-cell transcriptome analysis through meningioma malignancy, which included 18 samples spanning normal meninges, benign and high-grade in situ tumors, and lung metastases, for extensive transcriptome characterization. Tumor suppressor candidate gene and molecular mechanism were functionally validated at the animal model and cellular levels. Results Comprehensive analysis and validation in mice and clinical cohorts indicated clusterin (CLU) had suppressive function for meningioma tumorigenesis and malignancy by inducing mitochondria damage and triggering type 1 interferon pathway dependent on its secreted isoform, and the inhibition effect was enhanced by TNFα as TNFα also induced type 1 interferon pathway. Meanwhile, both intra- and extracellular CLU overexpression enhanced macrophage polarization towards M1 phenotype and TNFα production, thus promoting tumor killing and phagocytosis. Conclusions CLU might be a key brake of meningioma malignance by synchronously modulating tumor cells and their microenvironment. Our work provides comprehensive insights into meningioma malignancy and a potential therapeutic strategy.