Prometastatic Potential of Non-Functionalized Multiwalled Carbon Nanotubes in the MDA-MB-436 Breast Cancer Cell Line ModelMatysiak-Kucharek, Sawicki, Kruszewski
et alInt J Mol Sci (2025) 26 (6)
Abstract: Multiwalled carbon nanotubes (MWCNTs) are used in many areas of industry and medicine. However, there is evidence suggesting profibrogenic action of MWCNTs, probably via the epithelial-mesenchymal transition mechanism (EMT). The aim of this study was to evaluate the prometastatic activity of 5-20 nm and 50-80 nm MWCNTs against cells of the MDA-MB-436 line. We used MTT and NR assays to determine MWCNTs' cytotoxicity and the level of malonylodialdehyde and thiol compounds as indicators of oxidative stress. qRT-PCR was used to examine the expression of EMT markers. The QCM Chemotaxis Cell Migration Assay was used to assess cell migration, while the Cytokine Array Kit and Apoptosis Array Kit were used to determine cytokine expression and induction of apoptosis. The interleukin 6, C-X-C motif chemokine ligand 8, and tumor growth factor beta 1 (TGFB1) secretion was determined by ELISA. MWCNTs were toxic to MDA-MB-436 cells and induced cell death via the apoptosis pathway. MWCNTs induced a low level of oxidative stress and were associated with increased secretion of pro-inflammatory cytokines and chemokines, including proteins important in breast cancer metastasis. Cells incubated with MWCNTs showed increased expression of mesenchymal EMT markers. However, in contrast to these results, the migration of MWCNT-treated cells increased only modestly relative to untreated cells. Also, the secretion of TGFB1, a key inducer and regulator of EMT, increased only slightly. In summary, the multifaceted effect of MWCNTs on cancer cells encourages further work on the safety of nanomaterials.
Interplay Between TGFβ1 Signaling and Cancer-Testis Antigen MAGEB2: A New Thorn in Cancer's Side?Colemon, Romney, Jones
et alInt J Mol Sci (2025) 26 (6)
Abstract: The Melanoma Antigen Gene (MAGE) family of proteins is the largest family of cancer-testis antigens (CTAs) and shares a MAGE homology domain (MHD). MAGE proteins are divided into Type I and Type II MAGEs depending on their chromosomal location and expression patterns. Type I MAGEs are true CTAs. MAGEB2 is a Type I MAGE, belonging to the MAGEB subfamily, and unlike some MAGE proteins, has not been found to bind to and enhance E3 ligase activity. MAGEB2 has been discovered to be an RNA-binding protein that serves to protect spermatogonial cells in the testis from extraneous stressors. We have discovered that MAGEB2 is necessary and sufficient for the proliferation of cells and is expressed by the differential DNA methylation of its gene promoter. Furthermore, we identified JunD as the transcription factor that regulates MAGEB2 expression. When expressed, MAGEB2 suppresses transforming grown factor-β1 (TGFβ1) signaling by decreasing mRNA levels of Thrombospondin-1 (TSP-1). TSP-1 is an anti-angiogenic protein that activates TGFβ1. Restoring levels of TSP-1 or TGFβ1 results in the inability of MAGEB2 to drive proliferation, suggesting that MAGEB2-expressing tumors might be more susceptible to therapies that induce or activate TSP-1 or TGFβ1 signaling.
Association of the TGFB1 Gene Polymorphisms with Pain Symptoms and the Effectiveness of Platelet-Rich Plasma in the Treatment of Lateral Elbow Tendinopathy: A Prospective Cohort StudyJarosz, Wrona, Balcerzyk-Matić
et alInt J Mol Sci (2025) 26 (6)
Abstract: The regenerative properties of platelet-rich plasma (PRP) result from the high concentration of growth factors, including transforming growth factor beta 1 (TGF-β1). Nevertheless, this form of therapy may not always be effective due to the variability in genetic factors. In this study, the association of TGFB1 gene polymorphisms with the effectiveness of lateral elbow tendinopathy (LET) treatment with PRP was investigated. The effectiveness of therapy was assessed using minimal clinically important difference (MCID) and patient-reported outcome measures (PROM), specifically visual analog scale (VAS), quick version of disabilities of the arm, shoulder, and hand score (QDASH), and patient-rated tennis elbow evaluation (PRTEE) for two years (in weeks 2, 4, 8, 12, 24, 52, and 104). The most effective therapy was noticed in CC rs2278422 genotype carriers, whereas carriers of AA, CC, and CC genotypes (rs12461895, rs4803455, rs2241717) showed more severe pain before therapy. Moreover, the analyses revealed an association of studied polymorphisms with such parameters of blood morphology as eosinophils (EOS), neutrophils (NEU), and monocytes (MONO). In conclusion, genotyping of rs2278422 variant may be a valuable diagnostic method for patient selection for PRP therapy, while genotyping of rs12461895, rs4803455, and rs2241717 polymorphisms may be used for prediction of increased risk of pain sensation.
TGF-β Induces the Secretion of Extracellular Vesicles Enriched with CD39 and CD73 from Cervical Cancer CellsMolina-Castillo, Monroy-García, García-Rocha
et alInt J Mol Sci (2025) 26 (6)
Abstract: The presence of TGF-β in the tumor microenvironment of cervical cancer (CC) is important for tumor progression. In this study, we analyzed the effect of TGF-β on the expression of the ectonucleotidases CD39 and CD73, which are involved in the generation of adenosine (Ado), in CC cells and in extracellular vesicles (EVs) secreted by these cells. Treatment of HeLa and CaSki cells for 72 h with recombinant human TGF-β increased the expression of CD39 and CD73 by 20 and 30% and by 40 and 100%, respectively. The addition of SB505124, an inhibitor of the TGF-β1 receptor, or GW4869, an inhibitor of exosome formation and release, reduced the expression and release of both ectonucleotidases in CC cells. Furthermore, TGF-β promoted the secretion of medium-large EVs (>130 nm) in HeLa cells (HeLa + TGF-β/EVs) and CaSki cells (CaSki + TGF-β/EVs), which increased the expression of CD39 (>20%) and CD73 (>60%), and EVs obtained from cells treated with TGF-β had a greater capacity to generate Ado than did EVs obtained from cells cultured in the absence of this factor (HeLa/EVs and CaSki/EVs). These findings suggest that the production of TGF-β in the CC TME can promote neoplastic progression through the secretion of EVs enriched with CD39 and CD73. Therefore, the inhibition of CD39+ CD73+ EVs could be a strategy for the treatment of CC.
膜杰作
Star Staining
