Anticancer research最新文献

{"title":"Combination of Recombinant Methioninase With Rapamycin or Chloroquine Is Synergistic to Highly Inhibit Triple-negative Breast Cancer Cells <i>In Vitro</i>.","authors":"Jinsoo Kim, Qinghong Han, Byung Mo Kang, Kohei Mizuta, Yohei Asano, Michael Bouvet, Robert M Hoffman","doi":"10.21873/anticanres.17564","DOIUrl":"https://doi.org/10.21873/anticanres.17564","url":null,"abstract":"<p><strong>Background/aim: </strong>Triple-negative breast cancer (TNBC) is a highly aggressive and heterogeneous subtype of breast cancer with a poor prognosis despite multimodal treatment. New therapeutic approaches for TNBC are necessary. We very recently showed that the triple combination of recombinant methioninase (rMETase), rapamycin (RAPA), and chloroquine (CQ) synergically eradicated osteosarcoma cells <i>in vitro</i>. The present study aimed to determine whether rMETase has synergistic efficacy with either RAPA or CQ on a TNBC cell line.</p><p><strong>Materials and methods: </strong>The half-maximal inhibitory concentrations (IC₅₀) of rMETase, RAPA, and CQ were determined on the human MDA-MB-231 TNBC cell line <i>in vitro</i>. The efficacy of rMETase, combined with RAPA or with CQ, at their respective IC₅₀ values, on MDA-MB-231 cell viability was determined using the WST-8 assay.</p><p><strong>Results: </strong>The IC₅₀ of rMETase was 0.56 U/ml, for RAPA the IC₅₀ was 3.9 μM, and for CQ the IC₅₀ was 5.0 μM. The viability of the MDA-MB-231 cells was significantly decreased after treatment with rMETase plus RAPA or rMETase plus CQ, compared to the control cells or cells treated with one drug only.</p><p><strong>Conclusion: </strong>rMETase, when combined with either RAPA or CQ, is synergistic on the MDA-MB-231 TNBC cell line. The present findings suggest the potential for future clinical applications of rMETase plus chemotherapy, such as RAPA or CQ, for recalcitrant TNBC.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 5","pages":"1853-1859"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advantages and Disadvantages of Drug Combination Treatment: Riluzole, Metformin and Dexamethasone Effect on Glioblastoma Cell.","authors":"Jonathan Keul, Swetlana Sperling, Veit Rohde, Milena Ninkovic","doi":"10.21873/anticanres.17561","DOIUrl":"https://doi.org/10.21873/anticanres.17561","url":null,"abstract":"<p><strong>Background/aim: </strong>In glioblastoma multiforme (GBM), a deadly brain tumor, glucose is one of the main fuels for accelerated growth. Patients with GBM are also exposed to excess glucose through hyperglycemia in diabetes mellitus. In addition, dexamethasone (Dex), a corticosteroid commonly administered for controlling cerebral oedema, causes additional excess glucose. Therefore, targeting glucose metabolism is an attractive therapeutic intervention for GBM treatment. We have recently shown that riluzole (Ril), a drug used to treat amyotrophic lateral sclerosis (ALS), has an effect on some detrimental Dex-induced metabolic changes in GBM. Therefore, we examined the effect of the combination of metformin (Met), widely used to treat type 2 diabetes, and Ril on GBM cells.</p><p><strong>Materials and methods: </strong>The 3-(4, 5-dimethylthiazol)-2, 5-diphenyltetrazolium bromide (MTT) assay was used to determine cell viability of U87MG after treatment with Ril, Met, Ril plus Met (Ril+Met) and the addition of Dex to this co-treatment. Cell migration was assessed by the xCELLigence system, matrix metalloproteinase 2 (MMP2) activation by zymography assay and gene expression by real-time polymerase chain reaction (RT-PCR).</p><p><strong>Results: </strong>Co-treatment with Ril and Met was effective in killing GBM cells and reducing the expression of genes involved in glucose and stem cell metabolism. Furthermore, combination of Ril and Met reduced MMP2 activation. But co-administration increased the migration of U87MG cells. The addition of Dex to this combination reversed the unfavorable effects of Ril+Met on cell migration.</p><p><strong>Conclusion: </strong>Ril+Met co-treatment had a positive effect in terms of GBM cell death, decreased expression of genes involved in glucose metabolism and stemness, and reduced MMP2 activation. Disadvantage of Ril+Met treatment was increased cell migration. Taken together, these drug combinations may also allow the reduction of the concentration of Dex to minimize its side effects.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 5","pages":"1813-1823"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemotherapy-induced Moderate to Severe Peripheral Neuropathy in Patients Receiving Adjuvant Radiotherapy for Breast Cancer.","authors":"Dirk Rades, Tobias Bartscht, Achim Rody, Nathan Y Yu, Martin Ballegaard","doi":"10.21873/anticanres.17587","DOIUrl":"https://doi.org/10.21873/anticanres.17587","url":null,"abstract":"<p><strong>Background/aim: </strong>A significant number of breast cancer patients assigned to adjuvant radiotherapy receive pre- or postoperative chemotherapy that can cause peripheral sensory and autonomic neuropathy (PNP). Identifying and grading PNP using a mobile application (app) may facilitate early detection and management. This study evaluated the prevalence of pre-radiotherapy PNP, providing essential baseline data for the prospective validation of such an app.</p><p><strong>Patients and methods: </strong>Data of 133 breast cancer patients receiving chemotherapy prior to adjuvant radiotherapy were retrospectively analyzed regarding the incidence and risk factors of chemotherapy-induced moderate to severe PNP.</p><p><strong>Results: </strong>The incidence of moderate to severe PNP was 27.8%. On multivariate analysis, it was significantly associated with KPS ≤80 (<i>p</i>=0.030), history of significant cardiovascular disease (<i>p</i>=0.024), ≥10 pack years of smoking (<i>p</i>=0.023), and beta blocker medication (<i>p</i>=0.014). A trend was found for history of autoimmune disease (<i>p</i>=0.057).</p><p><strong>Conclusion: </strong>A considerable proportion of breast cancer patients assigned for adjuvant radiotherapy experienced moderate to severe PNP, which radiation oncologists should be aware of. The risk factors identified in this study likely contribute to earlier detection of PNP and inform the development of a prospective trial to validate a mobile-based PNP assessment tool.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 5","pages":"2123-2135"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of Plasminogen Activator Inhibitor-1 (PAI-1) by Tiplaxtinin Reduces Aggressiveness of Cervical Carcinoma Cells.","authors":"Sarah Wehbe, Julia Gallwas, Carsten Gründker","doi":"10.21873/anticanres.17559","DOIUrl":"https://doi.org/10.21873/anticanres.17559","url":null,"abstract":"<p><strong>Background/aim: </strong>The effect of G-protein-coupled estrogen receptor 1 (GPER1) on tumors depends on tumor entity, with its expression level influencing signal transduction and function. Recent research suggests that GPER1 promotes tumor suppression in cervical carcinoma (CC). In contrast, silencing GPER1 increases expression of serpin family E member 1 (<i>SERPINE1</i>) and its protein, plasminogen activator inhibitor-1 (PAI-1), and promotes tumor progression, raising the question of whether PAI-1 might be a suitable target for the treatment of CC. To explore this, we examined the impact of PAI-1 inhibition using Tiplaxtinin (PAI-039, TPX).</p><p><strong>Materials and methods: </strong>The effects of TPX treatment on viability, colony formation, migration, and invasion of SiHa cervical squamous cell carcinoma (CSCC) and HeLa cervical adenocarcinoma (CAC) cells were assessed using AlamarBlue, colony formation, gap closure, and Boyden chamber assays, respectively. Apoptosis was examined using the Annexin/PI assay, while the cell cycle was analyzed in more detail using the PI assay.</p><p><strong>Results: </strong>With increasing TPX concentration, viability and colony formation of SiHa and HeLa cells decreased significantly. Cell migration was strongly reduced under PAI-1 inhibitor treatment, while invasion showed a slight decline. Apoptosis and cell cycle were only minimally affected by TPX.</p><p><strong>Conclusion: </strong>PAI-1 inhibitor TPX showed a strong inhibitory effect on both SiHa CSCC and HeLa CAC cells, significantly reducing their viability, colony formation, and migratory capacity. The observed effects suggest that TPX could potentially be used to target and hinder the growth and spread of both CSCC and CAC cells.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 5","pages":"1793-1805"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of YAP1 and TAZ in Melanoma-, Bronchial- and Breast Carcinoma Brain Metastasis: Primary <i>vs.</i> Relapsed Tumors.","authors":"Jill Dicke, Laura Hero, Saskia Kuhl, Roland Goldbrunner, Marco Timmer","doi":"10.21873/anticanres.17560","DOIUrl":"https://doi.org/10.21873/anticanres.17560","url":null,"abstract":"<p><strong>Background/aim: </strong>Brain metastases from the most common primary sites - lung carcinoma, breast carcinoma, and melanoma - are more frequent than primary brain tumors. YAP1/TAZ are regulators of tissue growth and epithelial-mesenchymal transition (EMT) within the hippo pathway. The aim of the study was the evaluation of the role of YAP1/TAZ in brain metastasis.</p><p><strong>Materials and methods: </strong>Expression levels of YAP1 and TAZ were measured in samples of primary and relapsed brain metastases from patients with melanoma, breast carcinoma, and bronchial carcinoma using qPCR and western blot.</p><p><strong>Results: </strong>Expression of YAP1 and TAZ was highest in melanoma followed by bronchial carcinoma and lowest in breast carcinoma. For YAP1, expression in primary metastasis was higher than in relapsed metastasis.</p><p><strong>Conclusion: </strong>Because of the important role of YAP1/TAZ in EMT, targeting these genes could be a promising approach to reduce the risk of metastasis.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 5","pages":"1807-1812"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>HOX-PBX</i> Up-regulation Predicts Favorable Prognosis in NPM1-mutated Normal Cytogenetic AML <i>via</i> WNT Signaling.","authors":"Ghaleb Elyamany, Sultan Alotaibi, Bander Alharbi, Osama Atallah Alhafi, Hassan Aljasem, Hadi Jamil, Tariq M Roshan, Ariz Akhter, Adnan Mansoor","doi":"10.21873/anticanres.17582","DOIUrl":"https://doi.org/10.21873/anticanres.17582","url":null,"abstract":"<p><strong>Background/aim: </strong>Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy. <i>HOX</i> gene dysregulation, particularly within the <i>HOXA</i> cluster, plays a critical role in leukemogenesis. This study investigated the impact of <i>HOX-PBX</i> gene expression and its association with clinical outcomes in <i>NPM1</i>-mutated cytogenetically normal (CN)-AML.</p><p><strong>Materials and methods: </strong>Gene expression analysis was performed on diagnostic bone marrow samples from 35 CN-AML patients using the NanoString nCounter platform. Differential expression of <i>HOXA9, HOXA10</i>, and <i>PBX3</i> was assessed, along with correlations with <i>NPM1</i> mutation status and WNT pathway activation. Kaplan-Meier survival analysis was conducted to evaluate prognostic significance.</p><p><strong>Results: </strong><i>HOXA9</i> and <i>HOXA10</i> were significantly up-regulated in <i>NPM1</i>-mutated AML compared to NPM1-negative cases (<i>p</i><0.001). <i>PBX3</i> expression strongly correlated with <i>HOXA10</i> (r=0.86, <i>p</i><0.001), suggesting a cooperative role in leukemogenesis. Elevated <i>HOXA9</i> (>589.7) was associated with improved survival (hazard ratio=0.3, <i>p</i>=0.021). Up-regulated WNT pathway targets (<i>MYC, RUNX1</i>) in NPM1-mutated cases indicate active WNT/β-catenin signaling, potentially promoting differentiation and favorable prognosis.</p><p><strong>Conclusion: </strong><i>HOX-PBX-WNT</i> interactions contribute to the distinct biology of <i>NPM1</i>-mutated CN-AML. Targeting this axis may offer novel therapeutic strategies for AML, warranting further research into molecular-driven treatments for AML.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 5","pages":"2079-2089"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-related Survival Differences in Patients With Glioblastoma - Results From a Retrospective Analysis.","authors":"Jan Leppert, Claudia Ditz, Jakob Matschke, Harald Krenzlin, Naureen Keric, Christian Ziemann, Lorenz Hahn, Maria Vittoria Matone, Larysa Liubich, Karolin Streubel, Hannes Schacht, Christina Hillbricht, Patrick Kuppler, Dirk Rades, Anastassia Löser","doi":"10.21873/anticanres.17580","DOIUrl":"https://doi.org/10.21873/anticanres.17580","url":null,"abstract":"<p><strong>Background/aim: </strong>Glioblastoma is more common in men than in women. The aim of this analysis was to investigate sex-specific differences with a particular focus on their impact on survival including overall survival (OS) and progression-free survival (PFS).</p><p><strong>Patients and methods: </strong>This retrospective study analyzed 209 GBM patients (91 females, 118 males) treated according to the Stupp regimen. Data on patient demographics, O6-methylguanine-DNA methyltransferase (MGMT) methylation status, treatment details [radiotherapy (RT) doses and temozolomide (TMZ) cycles], and survival endpoints were statistically analyzed using univariable Kaplan-Meier [and 95% confidence intervals (CI)] and multivariable Cox regression hazards models.</p><p><strong>Results: </strong>In the whole cohort, median follow-up was 14 (2-119) months. We observed a trend towards a higher prevalence of multifocal tumors in males (30.5% <i>vs.</i> 22%, <i>p</i>=0.092). In univariable analysis, MGMT-negative male patients who received >58 Gy RT had a significantly longer OS (14 <i>vs.</i> 5 months, log-rank <i>p</i><0.001). In multivariable analysis, OS was not significantly influenced by patient age (<i>p</i>=0.579), total RT dose (Gy) (<i>p</i>=0.348), and MGMT status (<i>p</i>=0.262). Female patients (HR=3.252, <i>p</i>=0.028) and patients with higher tumor volume (HR=1.031, <i>p</i>=0.005) had a significantly higher mortality risk. Better Karnofsky-performance-status (HR=0.918, <i>p</i>=0.008), complete resection (HR=6.759, <i>p</i>=0.022), and higher numbers of adjuvant TMZ cycles (HR=0.739, <i>p</i>=0.003) led to prolonged OS.</p><p><strong>Conclusion: </strong>Sex seems to impact survival in patients suffering from glioblastoma, although underlying mechanisms are not yet completely understood. Treatment intensity (complete resection and the maximum possible number of TMZ cycles) had a significant effect on the patients' mortality risk.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 5","pages":"2059-2069"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiomics for Growth Prediction of Vestibular Schwannomas in Neurofibromatosis Type 2.","authors":"Nina Boe, Victor F Mautner, Reinhard E Friedrich, Said C Farschtschi, Lasse Dührsen, Hanno S Meyer, Johannes A Koeppen","doi":"10.21873/anticanres.17588","DOIUrl":"https://doi.org/10.21873/anticanres.17588","url":null,"abstract":"<p><strong>Background/aim: </strong><i>NF2</i>-related schwannomatosis, formerly known as Neurofibromatosis type 2 (NF2) is characterized by bilateral vestibular schwannomas (VS). Managing NF2 requires balancing watchful waiting with surgical intervention, each carrying inherent risks. While these risks are acknowledged, they have not yet been subjected to systematic investigation. Accurate prognosis of tumor growth is crucial for clinical decision-making. This study investigated radiomics features from longitudinal magnetic resonance imaging (MRI) data to predict VS growth.</p><p><strong>Patients and methods: </strong>Radiomics features were extracted from cranial MRIs of 32 NF2 patients, each with at least two or more imaging time points. The association between these features and tumor growth was analyzed through correlation, visual inspection, and the Boruta algorithm.</p><p><strong>Results: </strong>Correlations between growth rates and radiomics features were weak (ρ≤0.23, <i>p</i><0.016). Three features exhibited a bimodal distribution, with cluster affiliation linked to tumor growth rate [cluster A: 7.9%/month, cluster B: 2.0%/month; Fisher exact odds ratio (OR)=2.55, <i>p</i>=0.010]. When considering only the first tumors in the MRI series, the Fisher exact OR was 2.29 (<i>p</i>=0.223). Boruta analysis identified <i>wavelet.HLH_glcm_InverseVariance</i> as a key feature, also relevant in the bimodal distribution. The Fisher exact OR of <i>wavelet.HLH_glcm_InverseVariance</i> for tumor growth was 2.64 (<i>p</i>=0.011) for all tumors and 2.21 (<i>p</i>=0.229) for initial tumors in the MRI series.</p><p><strong>Conclusion: </strong>Bimodally distributed radiomics features from initial MRIs did not reliably predict rapid tumor growth (error probability: 23%) but may aid in planning MRI follow-up intervals.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 5","pages":"2137-2146"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Checkpoint Inhibitor-induced Uveitis: Disproportionality and Timing Analyses of the Japanese Pharmacovigilance Database.","authors":"Naohito Ide, Ken-Ichi Sako, Tomoji Maeda","doi":"10.21873/anticanres.17595","DOIUrl":"https://doi.org/10.21873/anticanres.17595","url":null,"abstract":"<p><strong>Background/aim: </strong>Immune checkpoint inhibitors (ICIs) are widely used anticancer drugs, but they can trigger immune-related adverse events (irAEs), including rare but potentially blinding uveitis. In this study, the associations between ICIs and uveitis, and the time to uveitis onset, were evaluated using data from the Japanese Adverse Drug Event Report (JADER) database.</p><p><strong>Patients and methods: </strong>We performed disproportionality analysis using data from the JADER database (April 2004-June 2024). Positive signals were identified using reporting odds ratios (RORs) with 95% confidence intervals (CIs). Time-to-onset analyses were performed with the Weibull distribution model, and sex-based differences were assessed with Kaplan-Meier curves and the log-rank test.</p><p><strong>Results: </strong>Among 914,713 cases in the JADER database, 346 were suspected ICI-induced uveitis. Positive signals were detected for nivolumab [ROR, 9.05 (95%CI=7.81-10.50)], ipilimumab [9.82 (8.20-11.76)], and pembrolizumab [4.94 (4.05-6.01)] but not for other ICIs. The median onset time was approximately 2 months (65 days for nivolumab, 61 days for ipilimumab, and 70 days for pembrolizumab). Pembrolizumab-induced uveitis occurred significantly earlier in female patients than in male patients (29.5 <i>vs.</i> 91 days, <i>p</i>=0.015). Onset patterns were classified as early failure for nivolumab and random failure for ipilimumab and pembrolizumab. The outcomes were mostly good, and severe cases of uveitis were rare.</p><p><strong>Conclusion: </strong>ICI-induced uveitis typically occurs within two months of treatment initiation, with pembrolizumab-induced uveitis occurring earlier in females than in males. Because causation cannot be established on the basis of this analysis, large-scale prospective clinical studies are needed.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 5","pages":"2215-2223"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Platelet Interactions in Promoting Melanoma Malignancy With Insights into Proliferation, Cyclin D1 Expression, and Migration.","authors":"Noriko Yoshikawa, Chinami Ikushima, Nanako Tanaka, Eriko Iwata, Kazuki Nakamura","doi":"10.21873/anticanres.17570","DOIUrl":"https://doi.org/10.21873/anticanres.17570","url":null,"abstract":"<p><strong>Background/aim: </strong>Metastasis is a major obstacle in cancer treatment and hematogenous metastasis plays a critical role in tumor progression. Platelets have been implicated in facilitating this process by interacting with circulating tumor cells, promoting immune evasion, extravasation, and metastatic colonization.</p><p><strong>Materials and methods: </strong>We explored the effects of platelet interactions on the malignancy of mouse melanoma cells, focusing on cell proliferation, cyclin D1 expression, and migration.</p><p><strong>Results: </strong>Co-culturing melanoma cells with platelets significantly increased their proliferative capacity, an effect that was also induced by the platelet culture supernatant alone. This suggests that soluble factors released from platelets, such as transforming growth factor-β (TGF-β) and platelet derived growth factor (PDGF), mediate this effect independently of direct cell-cell interactions. Furthermore, cyclin D1, a key regulator of the G₁/S phase transition, is up-regulated in melanoma cells upon exposure to platelet-derived factors, indicating enhanced cell cycle progression. Migration assays revealed the role of platelets in melanoma cell motility, whereas pre-treatment with platelets significantly increased their migratory ability in a transwell assay. This suggests that platelets enhanced cell motility <i>via</i> phenotypic changes and epithelial-mesenchymal transition in mouse melanoma cells.</p><p><strong>Conclusion: </strong>Platelets promote melanoma metastasis by enhancing cell proliferation and migration through soluble factor-mediated mechanisms. Targeting platelet-tumor interactions may represent a potential therapeutic strategy for mitigating metastatic progression.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 5","pages":"1927-1934"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}