Enhanced Tumorigenic Potential of Colorectal Cancer Cells by Extracellular Sulfatases

Vicente, Carolina Meloni; Lima, Marcelo A.; Yates, Edwin A.; Nader, Helena B.; Toma, Leny

doi:10.1158/1541-7786.mcr-14-0372

Cited by 22 publications

(28 citation statements)

References 51 publications

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“…This finding indicates that the observed modifications cannot be attributed exclusively to a depletion of SULF1 enzymatic activity, but also involves fine tuning of the HS structure through the biosynthesis machinery. Recently, a study on colorectal cancer cells over-expressing SULFs reported an increase in GlcNAc(6S)-containing disaccharides as a cellular response that compensates for the enzymatic driven decrease in [ΔUA(2S)-GlcNS(6S)] [59]. Our data support such complementary behavior, here in the context of SULF1 down-regulation by SDC1.…”

Section: Discussionsupporting

confidence: 82%

Syndecan-1 alters heparan sulfate composition and signaling pathways in malignant mesothelioma

Heidari-Hamedani

Vivès

Seffouh

et al. 2015

Cellular Signalling

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Syndecan-1 is a proteoglycan that acts as co-receptor through its heparan sulfate (HS) chains and plays important roles in cancer. HS chains are highly variable in length and sulfation pattern. This variability is enhanced by the SULF1/2 enzymes, which remove 6-O-sulfates from HS. We used malignant mesothelioma, an aggressive tumor with poor prognosis, as a model and demonstrated that syndecan-1 over-expression down-regulates SULF1 and alters the HS biosynthetic machinery. Biochemical characterization revealed a 2.7-fold reduction in HS content upon syndecan-1 over-expression, but an overall increase in sulfation. Consistent with low SULF1 levels, trisulfated disaccharides increased 2.5-fold. ERK1/2 activity was enhanced 6-fold. Counteracting ERK activation, Akt, WNK1, and c-Jun were inhibited. The net effect of these changes manifested in G1 cell cycle arrest. Studies of pleural effusions showed that SULF1 levels are lower in pleural malignancies compared to benign conditions and inversely correlate with the amounts of syndecan-1, suggesting important roles for syndecan-1 and SULF1 in malignant mesothelioma.

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Section: Discussionsupporting

confidence: 82%

Syndecan-1 alters heparan sulfate composition and signaling pathways in malignant mesothelioma

Heidari-Hamedani

Vivès

Seffouh

et al. 2015

Cellular Signalling

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“…HSPGs regulate signaling pathways important in cell proliferation, inflammation, angiogenesis, and invasion and are dysregulated in cancer (reviewed in (18) and (55)). As extracellular molecules, HSPGs and the extracellular enzymes that modify them, SULF2 and HPSE, are amenable to therapeutic targeting.…”

Section: Discussionmentioning

confidence: 99%

Heparan Sulfate Glycosaminoglycans in Glioblastoma Promote Tumor Invasion

Tran

Wade

McKinney

et al. 2017

Molecular Cancer Research

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Glioblastoma (GBM) is the most common primary malignant brain tumor of adults and confers a poor prognosis due, in part, to diffuse invasion of tumor cells. Heparan sulfate (HS) glycosaminoglycans, present on the cell surface and in the extracellular matrix, regulate cell signaling pathways and cell-microenvironment interactions. In GBM, the expression of HS glycosaminoglycans and the enzymes that regulate their function are altered but the actual HS content and structure are unknown. However, inhibition of HS glycosaminoglycan function is emerging as a promising therapeutic strategy for some cancers. In this study, we use liquid chromatography-mass spectrometry (LC/MS) analysis to demonstrate differences in HS disaccharide content and structure across four patient-derived tumorsphere lines (GBM1, 5, 6, 43) and between two murine tumorsphere lines derived from murine GBM with enrichment of mesenchymal and proneural gene expression (mMES and mPN, respectively) markers. In GBM, the heterogeneous HS content and structure across patient-derived tumorsphere lines suggested diverse functions in the GBM tumor microenvironment (TME). In GBM5 and mPN, elevated expression of sulfatase 2 (SULF2), an extracellular enzyme that alters ligand binding to HS, was associated with low trisulfated HS disaccharides, a substrate of SULF2. In contrast, other primary tumorsphere lines had elevated expression of the HS-modifying enzyme heparanase (HPSE). Using gene editing strategies to inhibit HPSE a role for HPSE in promoting tumor cell adhesion and invasion was identified. These studies characterize the heterogeneity in HS glycosaminoglycan content and structure across GBM and reveal their role in tumor cell invasion.

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“…PC-3 cells were washed with PBS and incubated in serum free culture medium containing a blocking DNA replication mitomycin C (10 µg/L) to avoid cell proliferation. The cells were wounded using 200 µl sterile pipette tips and then washed to remove detached cells and debris (28) and incubated in the absence (control, basal level of cellular function) and presence of 17β-estradiol (E2, 0.1 and 10 nM; Sigma Chemical Co.); ERβ-selective agonist DPN [10 nM; 2,3-bis(4-hydroxyphenyl)-propionitrile, Tocris Bioscience, Bristol, United Kingdom] and ERB-041 (10 nM; Sigma Chemical Co.) or ERα-selective agonist PPT [10 nM; 4,4' ,4"-(4-propyl-(1H)-pyrazole-1,3,5-triyl)trisphenol, Tocris Bioscience] for 24 h at 37 • C. The cells were also untreated or pretreated with ERβ-selective antagonist PHTPP [10 nM; 4-(2-phenyl-5,7-bis(trifluoromethyl)pyrazolo(1,5-a)pyrimidin-3-yl)phenol, Tocris Bioscience] or with a compound that disrupts the complex β-catenin-TCF/LEF transcription factor, PKF 118-310 (100 nM, Sigma-Aldrich Co) for 30 min. Incubation was continued in the absence and presence of DPN (10 nM) or ERB-041 (10 nM), for 24 h at 37 • C (18,21,22).…”

Section: Wound Healing Analysismentioning

confidence: 99%

Estrogen Receptors Promote Migration, Invasion and Colony Formation of the Androgen-Independent Prostate Cancer Cells PC-3 Through β-Catenin Pathway

2020

Self Cite

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Prostate cancer is initially dependent on the androgen, gradually evolves into an androgen-independent form of the disease, also known as castration-resistant prostate cancer (CRPC). At this stage, current therapies scantily improve survival of the patient. Androgens and estrogens are involved in normal prostate and prostate cancer development. The mechanisms by which estrogens/estrogen receptors (ERs) induce prostate cancer and promote prostate cancer progression have not yet been fully identified. Our laboratory has shown that androgen-independent prostate cancer cells PC-3 express both ERα and ERβ. The activation of ERβ increases the expression of β-catenin and proliferation of PC-3 cells. We now report that the activation of ERβ promotes the increase of migration, invasion and anchorage-independent growth of PC-3 cells. Furthermore, the activation of ERα also plays a role in invasion and anchorageindependent growth of PC-3 cells. These effects are blocked by pretreatment with PKF 118-310, compound that disrupts the complex β-catenin/TCF/LEF, suggesting that ERs/β-catenin are involved in all cellular characteristics of tumor development in vitro. Furthermore, PKF 118-310 also inhibited the upregulation of vascular endothelial growth factor A (VEGFA) induced by activation of ERs. VEGF also is involved on invasion of PC-3 cells. In conclusion, this study provides novel insights into the signatures and molecular mechanisms of ERβ in androgen-independent prostate cancer cells PC-3. ERα also plays a role on invasion and colony formation of PC-3 cells.

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Enhanced Tumorigenic Potential of Colorectal Cancer Cells by Extracellular Sulfatases

Cited by 22 publications

References 51 publications

Syndecan-1 alters heparan sulfate composition and signaling pathways in malignant mesothelioma

Syndecan-1 alters heparan sulfate composition and signaling pathways in malignant mesothelioma

Heparan Sulfate Glycosaminoglycans in Glioblastoma Promote Tumor Invasion

Estrogen Receptors Promote Migration, Invasion and Colony Formation of the Androgen-Independent Prostate Cancer Cells PC-3 Through β-Catenin Pathway

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