The close relationship between heparanase and epithelial mesenchymal transition in gastric signet-ring cell adenocarcinoma

Shah, Shahid; Fourgeaud, C.; Derieux, Simon; Mirshahi, S.; Contant, G.; Pimpie, Cynthia; Dico, Réa Lo; Pocard, Marc; Mirshahi, Massoud

doi:10.18632/oncotarget.26042

Cited by 15 publications

(14 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The characteristics of SRCA are its resistance to chemotherapy (2), tissues fibrosis and peritoneal invasion (3). Recently we reported the upregulated expression of heparanase in SRCA, which is involved in the acquisition of the mesenchymal phenotype and tumor cell malignancy (4). In the present study, it was also revealed that the epithelial-mesenchymal transition (EMT) process could be inhibited by suramin, an heparanase inhibitor.…”

Section: Introductionmentioning

confidence: 99%

Targeting the differentiation of gastric cancer cells (KATO‑III) downregulates epithelial‑mesenchymal and cancer stem cell markers

2019

Self Cite

View full text Add to dashboard Cite

The aim of the present study was to analyze the acquisition of the differentiated phenotype in the human gastric signet ring cell adenoma cancer KATO-III cell line in vitro . The morphology of KATO-III cells was explored by microcinematography. Different cytokines secreted by both adherent and non-adherent KATO-III cells into medium were observed. The cancer stem cell phenotypes were identified by reverse transcription-quantitative polymerase chain reaction using primers (E-Cad, Slug, Snail, vimentin, NANOG, NESTIN, OCT3/4 and C-X-C motif chemokine receptor 4) or antibodies [cluster of differentiation (CD)90 and CD117] by flow cytometry (FACS). The influence of the induction media for the differentiation of mesenchymal cells was studied through viability and proliferation assays, by evaluating gene expression and the expression of markers via FACS. Cell viability and cell cycle distribution were evaluated following the treatment of KATO-III with acetyl salicylic acid and using the induction media as an inhibitor of epithelial-mesenchymal transition (EMT) and heparanase. A total of 3 phenotypes of KATO-III were observed (adherent, non-adherent and cell cluster), which have internal potential for cell transition into one of the other phenotypes. KATO-III was differentiated into adipocyte-, chondrocyte-, osteocyte- and neurocyte-like cells by the induction media. Identification of the induced cells was conducted using cell dyes. Reduced mRNA expression of EMT-associated molecules, stem cell markers and heparanase was observed with acetyl salicylic acid and induction media. An inhibitory effect of acetyl salicylic acid and the induction media was also noted in regard to cell proliferation. In addition, acetyl salicylic acid induced G0/G1 phase cell cycle arrest in KATO-III cells. In conclusion, the induction of the differentiation of cancer stem cells into non-proliferating cells offers the possibility for novel drug design to overcome the issues associated with metastasis, drug resistance and systemic toxicity with improved therapeutic efficacy.

show abstract

Section: Introductionmentioning

confidence: 99%

Targeting the differentiation of gastric cancer cells (KATO‑III) downregulates epithelial‑mesenchymal and cancer stem cell markers

2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Heparanase degrades heparan sulfate chains and it contributes to ECM remodeling. Heparanase is eventually involved in ECM remodeling and EMT [ 44 , 45 ]. When heparanase is downregulated, it can inhibit tumor metastasis [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

“…Heparanase is eventually involved in ECM remodeling and EMT [ 44 , 45 ]. When heparanase is downregulated, it can inhibit tumor metastasis [ 44 , 45 ]. Previous studies from our laboratories showed that MMP-14 activity was inhibited by lumican in melanoma [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Lumican Inhibits In Vivo Melanoma Metastasis by Altering Matrix-Effectors and Invadopodia Markers

Καραμάνου

Franchi

Proult

et al. 2021

Cells

View full text Add to dashboard Cite

It was reported that lumican inhibits the activity of metalloproteinase MMP-14 and melanoma cell migration in vitro and in vivo. Moreover, Snail triggers epithelial-to-mesenchymal transition and the metastatic potential of cancer cells. Therefore, the aim of this study was to examine the effect of lumican on Mock and Snail overexpressing melanoma B16F1 cells in vivo. Lung metastasis was analyzed after intravenous injections of Mock-B16F1 and Snail-B16F1 cells in Lum+/+ and Lum−/− mice. At day 14, mice were sacrificed, and lungs were collected. The number of lung metastatic nodules was significantly higher in mice injected with Snail-B16F1 cells as compared to mice injected with Mock-B16F1 cells confirming the pro-metastatic effect of Snail. This effect was stronger in Lum−/− mice as compared to Lum+/+, suggesting that endogenous lumican of wild-type mice significantly inhibits metastasis to lungs. Scanning electron and confocal microscopy investigations demonstrated that lumican inhibits the development of elongated cancer cell phenotypes which are known to develop invadopodia releasing MMPs. Moreover, lumican was shown to affect the expression of cyclin D1, cortactin, vinculin, hyaluronan synthase 2, heparanase, MMP-14 and the phosphorylation of FAK, AKT, p130 Cas and GSK3α/β. Altogether, these data demonstrated that lumican significantly inhibits lung metastasis in vivo, as well as cell invasion in vitro, suggesting that a lumican-based strategy targeting Snail-induced metastasis could be useful for melanoma treatment.

show abstract

“…Examples include suramin for prostate cancer [71], inhibition of inducible nitric oxide synthase for triple negative breast cancer [72], and chitosan as a nanocarrier for SN38 and Snail-specific siRNA in prostate cancer cells [73]. These approaches have been shown to downregulate Twist [72], Slug [72,74], and Snail [72,73]. Furthermore, the crosstalk between tumour cells undergoing EMT and immune cells in the tumour microenvironment has garnered increasing interest and may provide possibilities for combining immunotherapy with EMTtargeted therapy or for using EMT score as a potential predictive marker for immunotherapy response [75,76].…”

Section: Discussionmentioning

confidence: 99%

The epithelial–mesenchymal transition regulators Twist, Slug, and Snail are associated with aggressive tumour features and poor outcome in prostate cancer patients

Børretzen

Gravdal

Haukaas

et al. 2021

The Journal of Pathology CR

View full text Add to dashboard Cite

The prognostic importance of transcription factors promoting epithelial-mesenchymal transition (EMT) and angiogenesis has not been well explored in prostate cancer patients with long follow-up, nor the interplay between these factors. The objective of this study was to assess the individual protein expression and coexpression of Twist, Slug (Snai2), Snail (Snai1), and hypoxia-inducible factor-1 alpha (Hif-1α) in prostate cancer in relation to EMT, angiogenesis, hypoxia, tumour features, disease recurrence, and patient survival. Immunohistochemical staining was performed on tissue microarray sections from 338 radical prostatectomies with long follow-up. In addition, 41 cases of prostatic hyperplasia, 33 non-skeletal metastases, 13 skeletal metastases, and 33 castration-resistant prostate carcinomas were included. Our findings were validated in external gene expression data sets. Twist was overexpressed in primary prostate cancer and markedly reduced in distant metastases (p < 0.0005). Strong expression of Twist and Slug was associated with Hif-1α in localised prostate cancer (p ≤ 0.001), and strong Twist was associated with Hif-1α in castration-resistant carcinomas (p = 0.044). Twist, Slug, and increased Snail at the tumour stromal border were associated with vascular factors (p ≤ 0.045). Each of the three EMT-regulating transcription factors were associated with aggressive tumour features and shorter time to recurrence and cancer-specific death. Notably, the co-expression of factors demonstrated an enhanced influence on outcome. In the subgroup of E-cadherin low carcinomas, strong Slug was associated with shorter time to all end points and was an independent predictor of time to multiple end points, including cancer-specific death (hazard ratio 3.0, p = 0.041). To conclude, we demonstrate an important relation between EMT, hypoxia, and angiogenesis and a strong link between the investigated EMT regulators and aggressive tumour features and poor patient outcome in prostate cancer. Despite the retrospective nature of this long-term study, our findings could have a significant impact on the future treatment of prostate cancer, where tailored therapies might be directed simultaneously against epithelial-mesenchymal phenotypes, angiogenesis, and tumour hypoxia.

show abstract

The close relationship between heparanase and epithelial mesenchymal transition in gastric signet-ring cell adenocarcinoma

Cited by 15 publications

References 42 publications

Targeting the differentiation of gastric cancer cells (KATO‑III) downregulates epithelial‑mesenchymal and cancer stem cell markers

Targeting the differentiation of gastric cancer cells (KATO‑III) downregulates epithelial‑mesenchymal and cancer stem cell markers

Lumican Inhibits In Vivo Melanoma Metastasis by Altering Matrix-Effectors and Invadopodia Markers

The epithelial–mesenchymal transition regulators Twist, Slug, and Snail are associated with aggressive tumour features and poor outcome in prostate cancer patients

Contact Info

Product

Resources

About