Assessment of the SRC Inhibition Role in the Efficacy of Breast Cancer Radiotherapy

Shahrokh, Shabnam; Mansouri, Vahid; Razzaghi, Mohammadreza

doi:10.15171/jlms.2019.s4

Cited by 3 publications

(2 citation statements)

References 26 publications

(22 reference statements)

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“…Therefore, the interaction between EOC and the mesothelial cells is critical for the formation of peritoneal metastasis [23]. It is at this point that the primary mesothelial cells express FN1, which binds to the extracellular domain of CSPG4 [24]. Previous studies have revealed that the TGF-β secreted by EOC cells in malignant ascites alters the conditions of the mesothelial cells [20,25].…”

Section: Discussionmentioning

confidence: 99%

Chondroitin Sulfate Proteoglycan 4 Provides New Treatment Approach to Preventing Peritoneal Dissemination in Ovarian Cancer

Uno,

Koya,

Yoshihara

et al. 2024

IJMS

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Most epithelial ovarian cancer (EOC) patients are diagnosed with peritoneal dissemination. Cellular interactions are an important aspect of EOC cells when they detach from the primary site of the ovary. However, the mechanism remains underexplored. Our study aimed to reveal the role of chondroitin sulfate proteoglycan 4 (CSPG4) in EOC with a major focus on cell–cell interactions. We examined the expression of CSPG4 in clinical samples and cell lines of EOC. The proliferation, migration, and invasion abilities of the CSPG4 knockdown cells were assessed. We also assessed the role of CSPG4 in spheroid formation and peritoneal metastasis in an in vivo model using sh-CSPG4 EOC cell lines. Of the clinical samples, 23 (44.2%) samples expressed CSPG4. CSPG4 was associated with a worse prognosis in patients with advanced EOC. Among the EOC cell lines, aggressive cell lines, including ES2, expressed CSPG4. When CSPG4 was knocked down using siRNA or shRNA, the cell proliferation, migration, and invasion abilities were significantly decreased compared to the control cells. Proteomic analyses showed changes in the expression of proteins related to the cell movement pathways. Spheroid formation was significantly inhibited when CSPG4 was inhibited. The number of nodules and the tumor burden of the omentum were significantly decreased in the sh-CSPG4 mouse models. In the peritoneal wash fluid from mice injected with sh-CSPG4 EOC cells, significantly fewer spheroids were present. Reduced CSPG4 expression was observed in lymphoid enhancer-binding factor 1-inhibited cells. CSPG4 is associated with aggressive features of EOC and poor prognosis. CSPG4 could be a new treatment target for blocking peritoneal metastasis by inhibiting spheroid formation.

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Section: Discussionmentioning

confidence: 99%

Chondroitin Sulfate Proteoglycan 4 Provides New Treatment Approach to Preventing Peritoneal Dissemination in Ovarian Cancer

Uno,

Koya,

Yoshihara

et al. 2024

IJMS

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“…GSN is an actin binding protein, a key regulator of actin filament assembly and disassembly, and is involved in cell movement, shape, and metabolism (Feldt et al, 2019). Studies have shown that GSN gene transcription is down-regulated in breast cancer of humans and some animals, and the activation of GSN may be a protective factor in the treatment of cancer cells against cancer (Mielnicki et al, 1999;Shahrokh et al, 2019). The secreted GSN inhibits the invasion and migration of colon cancer cells (Chen et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Discovered Key CpG Sites by Analyzing DNA Methylation and Gene Expression in Breast Cancer Samples

Cao

Liu

2022

Front. Cell Dev. Biol.

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Breast cancer is the most common cancer in the world, and DNA methylation plays a key role in the occurrence and development of breast cancer. However, the effect of DNA methylation in different gene functional regions on gene expression and the effect of gene expression on breast cancer is not completely clear. In our study, we computed and analyzed DNA methylation, gene expression, and clinical data in the TCGA database. Firstly, we calculated the distribution of abnormal DNA methylated probes in 12 regions, found the abnormal DNA methylated probes in down-regulated genes were highly enriched, and the number of hypermethylated probes in the promoter region was 6.5 times than that of hypomethylated probes. Secondly, the correlation coefficients between abnormal DNA methylated values in each functional region of differentially expressed genes and gene expression values were calculated. Then, co-expression analysis of differentially expressed genes was performed, 34 hub genes in cancer-related pathways were obtained, of which 11 genes were regulated by abnormal DNA methylation. Finally, a multivariate Cox regression analysis was performed on 27 probes of 11 genes. Three DNA methylation probes (cg13569051 and cg14399183 of GSN, and cg25274503 of CAV2) related to survival were used to construct a prognostic model, which has a good prognostic ability. Furthermore, we found that the cg25274503 hypermethylation in the promoter region inhibited the expression of the CAV2, and the hypermethylation of cg13569051 and cg14399183 in the 5′UTR region inhibited the expression of GSN. These results may provide possible molecular targets for breast cancer.

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Chondroitin sulfate proteoglycan 4 provides new treatment approach to prevent peritoneal dissemination in ovarian cancer

Uno

Koya

Yoshihara

et al. 2023

Preprint

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BACKGROUND: Most epithelial ovarian cancer (EOC) patients are diagnosed with peritoneal dissemination. Cellular interactions are an important aspect to induce peritoneal disseminations. Our study aimed to reveal the role of chondroitin sulfate proteoglycan 4 (CSPG4) in EOC with a major focus on cell-cell interactions. METHODS: We examined the expression of CSPG4 in clinical samples. The proliferation, migration, and invasion abilities of the CSPG4-knockdown cells were assessed. We also assessed the role of CSPG4 in spheroid formation and peritoneal metastasis in vivo model using sh-CSPG4 EOC cell lines. RESULTS: Of clinical samples, 23 (44.2%) samples were expressed CSPG4. CSPG4 was associated with a worse prognosis in EOC patients. When CSPG4 was knockdown, the cell proliferation, migration, and invasion abilities were significantly decreased, and spheroid formation was significantly inhibited compared to control cells. Proteomic analyses showed changes in the expression of proteins related to cell movement pathways. The number of peritoneal disseminations and EOC spheroids in ascites were significantly decreased in sh-CSPG4 mouse models. Reduced CSPG4 expression was observed in lymphoid enhancer-binding factor1-inhibited cell. CONCLUSION: CSPG4 is associated with aggressive features of EOC and poor prognosis. CSPG4 could be a new treatment target to block peritoneal metastasis.

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Assessment of the SRC Inhibition Role in the Efficacy of Breast Cancer Radiotherapy

Cited by 3 publications

References 26 publications

Chondroitin Sulfate Proteoglycan 4 Provides New Treatment Approach to Preventing Peritoneal Dissemination in Ovarian Cancer

Chondroitin Sulfate Proteoglycan 4 Provides New Treatment Approach to Preventing Peritoneal Dissemination in Ovarian Cancer

Discovered Key CpG Sites by Analyzing DNA Methylation and Gene Expression in Breast Cancer Samples

Chondroitin sulfate proteoglycan 4 provides new treatment approach to prevent peritoneal dissemination in ovarian cancer

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