Showing papers by "Charles J. Dimitroff published in 2023"

The pleiotropic role of galectin-3 in melanoma progression: Unraveling the enigma.

Abstract: Melanoma is a highly aggressive skin cancer with poor outcomes associated with distant metastasis. Intrinsic properties of melanoma cells alongside the crosstalk between melanoma cells and surrounding microenvironment determine the tumor behavior. Galectin-3 (Gal-3), a ß-galactoside-binding lectin, has emerged as a major effector in cancer progression, including melanoma behavior. Data from melanoma models and patient studies reveal that Gal-3 expression is dysregulated, both intracellularly and extracellularly, throughout the stages of melanoma progression. This review summarizes the most recent data and hypotheses on Gal-3 and its tumor-modulating functions, highlighting its role in driving melanoma growth, invasion, and metastatic colonization. It also provides insight into potential Gal-3-targeted strategies for melanoma diagnosis and treatment.

Galectins can serve as biomarkers in COVID-19: A comprehensive systematic review and meta-analysis

Abstract: Background Galectins are an eleven-member class of lectins in humans that function as immune response mediators and aberrancies in their expression are commonly associated with immunological diseases. Several studies have focused on galectins as they may represent an important biomarker and a therapeutic target in the fight against COVID-19. This systematic review and meta-analysis examined the usefulness of clinical assessment of circulating galectin levels in patients with COVID-19. Methods International databases including PubMed, Scopus, Web of Science, and Embase were systematically used as data sources for our analyses. The random-effect model was implemented to calculate the standardized mean difference (SMD) and a 95% confidence interval (CI). Results A total of 18 studies, comprising 2,765 individuals, were identified and used in our analyses. We found that Gal-3 is the most widely investigated galectin in COVID-19. Three studies reported significantly higher Gal-1 levels in COVID-19 patients. Meta-analysis revealed that patients with COVID-19 had statistically higher levels of Gal-3 compared with healthy controls (SMD 0.53, 95% CI 0.10 to 0.96, P=0.02). However, there was no significant difference between severe and non-severe cases (SMD 0.45, 95% CI -0.17 to 1.07, P=0.15). While one study supports lower levels of Gal-8 in COVID-19, Gal-9 was measured to be higher in patients and more severe cases. Conclusion Our study supports Gal-3 as a valuable non-invasive biomarker for the diagnosis and/or prognosis of COVID-19. Moreover, based on the evidence provided here, more studies are needed to confirm a similar diagnostic and prognostic role for Gal-1, -8, and -9.

Abstract 3602: The metastasis-suppressive function of intracellular galectin-3 in melanoma

Abstract: Melanoma is a relatively rare skin cancer. However, it accounts for most of all skin cancer-related deaths worldwide. Once melanoma spreads to distant sites, it confers a poor prognosis characterized by resistance to therapy and high mortality rate. Hence, a favorable clinical outcome is strongly correlated with early diagnosis. Despite the ongoing research to identify novel diagnostic, prognostic, and therapeutic targets for metastatic melanoma (MM), a reliable serum marker to predict whether melanoma is vulnerable to metastasize or has already metastasized is still lacking. Galectin-3 (Gal-3), a ß-galactoside-binding protein, is widely expressed by many human epithelial and immune cells. High extracellular Gal-3 expression levels have been reported to be positively correlated with late-stage disease in melanoma patients, where it is theorized to bind surface glycosylated proteins to promote melanoma cell invasion and metastasis. Gal-3 is also expressed intracellularly where it participates in the regulation of many biological processes. However, intrinsic Gal-3 levels within the melanoma cell and its relationship to melanoma progression is still poorly understood. Using The Cancer Genome Atlas (TCGA) database, we analyzed the Gal-3 expression profiles of 471 tumor samples obtained from melanoma patients. To our surprise, TCGA data analysis has shown significantly higher expression of Gal-3 in primary melanoma samples compared to metastatic melanoma. We hypothesize that intracellular Gal-3 potentially negatively regulates primary melanoma progression to metastatic disease. Using several human melanoma cell lines silenced for Gal-3 expression, we investigated the corresponding malignancy-associated activities of these cells. Our results revealed that Gal-3 silencing in melanoma cells potentiated melanoma migration, invasion, and colony formation, compared with mock controls, suggesting that intracellular Gal-3 could interfere with melanoma metastatic activity. Moreover, loss of Gal-3 boosted the activation of the PI3K/AKT and MAPK signaling pathways and upregulated nuclear factor of activated T cells (NFAT1) expression and its pro-metastatic downstream target genes. Importantly, this study illuminates the apparent opposing roles of Gal-3 in melanoma progression, with intracellular Gal-3 potentially serving as a metastasis-suppressive molecule. Moreover, these studies reveal the potential of analyzing melanoma cell-intrinsic levels of Gal-3 to better predict metastatic potential and clinical outcome in melanoma patients. Citation Format: Norhan B. B. Mohammed, Charles J. Dimitroff. The metastasis-suppressive function of intracellular galectin-3 in melanoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3602.