Mesenchymal stem cells, also known as multipotent stromal progenitor cells, can differentiate into cells of mesodermal lineage. Gangliosides are sialic acid-conjugated glycosphingolipids that are believed to regulate cell differentiation and several signaling molecules. These molecules are localized in glycosphingolipid-enriched microdomains on the cell surface and are regulated by glycosphingolipid composition. Transforming growth factor-beta (TGF-β) signaling plays a critical role in chondrogenic differentiation. However, the role of gangliosides in chondrogenesis is not understood. In this study, the relationship between the ganglioside GM3 and TGF-β activation, during chondrogenic differentiation, was investigated using an aggregate culture of human synovial membrane-derived mesenchymal stem cells. We showed that the gangliosides GM3 and GD3 were expressed after the chondrogenic differentiation of hSMSC aggregates. To test whether GM3 affected the chondrogenic differentiation of hSMSC aggregates, we used GM3 treatment during chondrogenic differentiation. The results showed that the group treated with 5 μM GM3 had higher expression of chondrogenic specific markers, increased toluidine blue, and safranin O staining, and increased accumulation of glycosaminoglycans compared with the untreated group. Furthermore, GM3 treatment enhanced TGF-β signaling via SMAD 2/3 during the chondrogenic differentiation of hSMSC aggregates. Taken together, our results suggested that GM3 may be useful in developing therapeutic agents for cell-based articular cartilage regeneration in articular cartilage disease.

Production of therapeutic monoclonal antibodies (mAbs) using a plant platform has been considered an alternative to the mammalian cell-based production system. A plant-derived mAb CO17-1AK (mAb P COK) can specifically bind to various types of cancer cell lines. The target protein of mAb P COK is the epithelial cell adhesion molecule (EpCAM) highly expressed in human epithelial cancer cells, including breast and colorectal cancer cells. It has been hypothesized that its overexpression supports tumor growth and metastasis. A ganglioside is extended well beyond the surfaces of the various cell membranes and has roles in cell growth, inflammation, differentiation, and carcinogenesis. However, the regulation of EpCAM gene expression in breast cancers and the role of gangliosides in oncogenesis are unclear. Here, the purpose of this study was to determine the effects of mAb P COK on human breast cancer cell proliferation, apoptosis, and ganglioside expression patterns. Our results show that treatment with mAb P COK suppressed the growth of breast cancer cells and induced apoptotic cell death. It also upregulated the expression of metastasis-related gangliosides in breast cancer cells. Thus, treatment with mAb P COK may have chemo-preventive therapeutic effects against human breast cancer.

Malignant melanoma is a skin cancer with poor prognosis and high resistance to conventional treatment. 7,8-dihydroxyflavone (7,8-DHF) has shown anti-carcinogenic, anti-inflammatory, anti-oxidant, and pharmacological effects in several types of cancer. However, the relationship between ganglioside expression and the anti-cancer effects of 7,8-DHF in melanoma is not fully understood. In the present study, 7,8-DHF exhibits specific anti-proliferation, anti-migration, and G2/M phase cell-cycle arrest effects on both melanoma cancer cell lines, and induces mitochondrial dysfunction and apoptosis, making it a potent candidate for anti-melanoma treatment. Furthermore, we confirmed that 7,8-DHF significantly reduces the expression levels of ganglioside GD3 and its synthase, which are known to be closely involved in carcinogenesis. Taken together, our findings suggest that 7,8-DHF may be a potent anti-cancer drug candidate for the treatment of malignant melanoma.

This study aimed to investigate the effects of the human macrophage (MP) secretome in cellular xenograft rejection. The role of human nucleoside diphosphate kinase A (hNME1), from the secretome of MPs involved in the neuronal differentiation of miniature pig adipose tissue-derived mesenchymal stem cells (mp AD-MSCs), was evaluated by proteomic analysis. Herein, we first demonstrate that hNME1 strongly binds to porcine ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 (pST8SIA1), which is a ganglioside GD3 synthase. When hNME1 binds with pST8SIA1, it induces degradation of pST8SIA1 in mp AD-MSCs, thereby inhibiting the expression of ganglioside GD3 followed by decreased neuronal differentiation of mp AD-MSCs. Therefore, we produced nanobodies (NBs) named NB-hNME1 that bind to hNME1 specifically, and the inhibitory effect of NB-hNME1 was evaluated for blocking the binding between hNME1 and pST8SIA1. Consequently, NB-hNME1 effectively blocked the binding of hNME1 to pST8SIA1, thereby recovering the expression of ganglioside GD3 and neuronal differentiation of mp AD-MSCs. Our findings suggest that mp AD-MSCs could be a potential candidate for use as an additive, such as an immunosuppressant, in stem cell transplantation.

Malignant melanoma is one of the most progressive skin cancers, with a poor prognosis, various side effects, and high resistance to conventional treatment. Recently, 7,8-dihydroxyflavone (7,8-DHF), a polyphenolic flavonoid derived from certain plants, has been studied for its anti-carcinogenic, anti-inflammatory, antioxidant, and pharmacological effects in several types of cancer. Ganglioside, a modulator of diverse cell signals on the microdomain of the surface of the cell membrane, is closely involved in various cancers such as neuroblastoma. However, the correlation between ganglioside expression and the anti-cancer effects of 7,8-DHF in malignant melanoma remains unclear. In this study, 7,8-DHF showed potential as an anti-cancer agent through specific anti-proliferation, anti-oxidant, anti-migration, pro-apoptotic, and G2/M phase cell cycle arrest effects on SK-MEL-2 and G-361 melanoma cells. In contrast, 7,8-DHF did not induce cytotoxicity in non-tumoral epidermal HaCaT cells. Additionally, we confirmed for the first time that 7,8-DHF significantly reduces the expression levels of ganglioside GD3, which is closely involved in carcinogenesis, in both melanoma cancer cell lines using high-performance thin-layer chromatography analysis. Taken together, our findings suggest that 7,8-DHF might be a potent anticancer drug candidate for the treatment of malignant melanoma.