Sulfatase-1 overexpression indicates poor prognosis in urothelial carcinoma of the urinary bladder and upper tract

Lee, Hsiang Ying; Yeh, Bi-Wen; Chan, Ti Chun; Yang, Kei Fu; Li, Wei Ming; Huang, Ching‐Wen; Ke, Hung‐Lung; Li, Ching Chia; Yeh, Hsin Chih; Liang, Peir‐In; Shiue, Yow Ling; Wu, Wen‐Jeng; Li, Chien‐Feng

doi:10.18632/oncotarget.17590

Cited by 30 publications

(26 citation statements)

References 42 publications

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“…The other upregulated genes in the top-10 for all three organoids were CYP3A4 (a key enzyme for drug metabolism), the serine protease PRSS33 , AC008555.1 , AC008555.2 , and SULF1 . SULF1 is a multitask protein with roles at the plasma membrane and cell nucleus that has both tumor suppressor and promotor actions [ 52 , 53 , 54 ].…”

Section: Resultsmentioning

confidence: 99%

Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue

Costales-Carrera

Fernández‐Barral

Bustamante-Madrid

et al. 2020

Cancers

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Colon and rectal tumors, often referred to as colorectal cancer, show different gene expression patterns in studies that analyze whole tissue biopsies containing a mix of tumor and non-tumor cells. To better characterize colon and rectal tumors, we investigated the gene expression profile of organoids generated from endoscopic biopsies of rectal tumors and adjacent normal colon and rectum mucosa from therapy-naive rectal cancer patients. We also studied the effect of vitamin D on these organoid types. Gene profiling was performed by RNA-sequencing. Organoids from a normal colon and rectum had a shared gene expression profile that profoundly differed from that of rectal tumor organoids. We identified a group of genes of the biosynthetic machinery as rectal tumor organoid-specific, including those encoding the RNA polymerase II subunits POLR2H and POLR2J. The active vitamin D metabolite 1α,25-dihydroxyvitamin D3/calcitriol upregulated stemness-related genes (LGR5, LRIG1, SMOC2, and MSI1) in normal rectum organoids, while it downregulated differentiation marker genes (TFF2 and MUC2). Normal colon and rectum organoids share similar gene expression patterns and respond similarly to calcitriol. Rectal tumor organoids display distinct and heterogeneous gene expression profiles, with differences with respect to those of colon tumor organoids, and respond differently to calcitriol than normal rectum organoids.

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Section: Resultsmentioning

confidence: 99%

Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue

Costales-Carrera

Fernández‐Barral

Bustamante-Madrid

et al. 2020

Cancers

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“…For example, while the accumulation of perlecan initially functions as a tissue barrier to slow metastatic spread [50], it simultaneously increases the availability of heparan sulfate chains that stabilize factors that can enhance tumorigenicity. Similarly, even though silencing of SULF1 has been mostly associated with poor prognosis in a variety of carcinomas [33,[51][52][53], we hypothesize that these outcomes rely heavily on the signaling context, such as type of tumor, disease stage, spatial distribution of GAGases, specific ligands, and other factors [32]. In fact, SULF1 has displayed tumor-promoting activity in pancreatic, urothelial, and gastric cancers [51,54,55], which further highlights the complex outcomes of SULF1 activity in vivo.…”

Section: Discussionmentioning

confidence: 92%

SULF1 suppresses Wnt3A-driven growth of bone metastatic prostate cancer in perlecan-modified 3D cancer-stroma-macrophage triculture models

et al. 2020

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Bone marrow stroma influences metastatic prostate cancer (PCa) progression, latency, and recurrence. At sites of PCa bone metastasis, cancer-associated fibroblasts and tumor-associated macrophages interact to establish a perlecan-rich desmoplastic stroma. As a heparan sulfate proteoglycan, perlecan (HSPG2) stores and stabilizes growth factors, including heparin-binding Wnt3A, a positive regulator of PCa cell growth. Because PCa cells alone do not induce CAF production of perlecan in the desmoplastic stroma, we sought to discover the sources of perlecan and its growth factor-releasing modifiers SULF1, SULF2, and heparanase in PCa cells and xenografts, bone marrow fibroblasts, and macrophages. SULF1, produced primarily by bone marrow fibroblasts, was the main glycosaminoglycanase present, a finding validated with primary tissue specimens of PCa metastases with desmoplastic bone stroma. Expression of both HSPG2 and SULF1 was concentrated in αSMA-rich stroma near PCa tumor nests, where infiltrating pro-tumor TAMs also were present. To decipher SULF1's role in the reactive bone stroma, we created a bone marrow biomimetic hydrogel incorporating perlecan, PCa cells, macrophages, and fibroblastic bone marrow stromal cells. Finding that M2-like macrophages increased levels of SULF1 and HSPG2 produced by fibroblasts, we examined SULF1 function in Wnt3A-mediated PCa tumoroid growth in tricultures. Comparing control or SULF1 knockout fibroblastic cells, we showed that SULF1 reduces Wnt3A-driven growth, cellularity, and cluster number of PCa cells in our 3D model. We conclude that SULF1 can suppress Wnt3A-driven growth signals in the desmoplastic stroma of PCa bone metastases, and SULF1 loss favors PCa progression, even in the presence of pro-tumorigenic TAMs.

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“…For example, while the accumulation of perlecan 201 initially functions as a tissue barrier to slow metastatic spread [48], it simultaneously 202 increases the availability of heparan sulfate chains that stabilize factors that can 203 enhance tumorigenicity. Similarly, even though silencing of SULF1 has been mostly 204 associated with poor prognosis in a variety of carcinomas [31,[49][50][51], we hypothesize 205 that these outcomes rely heavily on the signaling context, such as type of tumor, disease 206 stage, spatial distribution of GAGases, specific ligands, and other factors [30]. In fact, 207 SULF1 has displayed tumor-promoting activity in pancreatic, urothelial, and gastric 208 cancers [49,52,53], which further highlights the complex outcomes of SULF1 activity in 209 vivo.…”

mentioning

confidence: 99%

“…stroma of primary prostate tumors[15], its cellular source(s) remained undetermined 48. In this study, we identified the cells that produce perlecan and its major enzyme49 modifier SULF1 and their respective roles in regulating Wnt3A-induced growth of50 metastatic PCa cells growing in perlecan-rich desmoplastic stroma, such as would occur 51 at sites of bone metastasis 52. February 26, 2020 2/21…”

mentioning

confidence: 99%

SULF1 suppresses Wnt3A-driven growth of bone metastatic prostate cancer in perlecan-modified 3D cancer-stroma-macrophage triculture models

Costa

Lewis

Truong

et al. 2020

Preprint

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Bone marrow stroma influences metastatic prostate cancer (PCa) progression, latency, and recurrence. At sites of PCa bone metastasis, cancer-associated fibroblasts and tumor-associated macrophages interact to establish a perlecan-rich desmoplastic stroma. As a heparan sulfate proteoglycan, perlecan (HSPG2 ) stores and stabilizes growth factors, including heparin-binding Wnt3A, a positive regulator of PCa cell growth. Because PCa cells alone do not induce CAF production of perlecan in the desmoplastic stroma, we sought to discover the sources of perlecan and its growth factor-releasing modifiers SULF1, SULF2, and heparanase in PCa cells and xenografts, bone marrow fibroblasts, and macrophages. SULF1, produced primarily by bone marrow fibroblasts, was the main glycosaminoglycanase present, a finding validated with primary tissue specimens of PCa metastases with desmoplastic bone stroma. Expression of both HSPG2 and SULF1 was concentrated in αSMA-rich stroma near PCa tumor nests, where infiltrating pro-tumor TAMs also were present. To decipher SULF1's role in the reactive bone stroma, we created a bone marrow biomimetic hydrogel incorporating perlecan, PCa cells, macrophages, and fibroblastic bone marrow stromal cells. Finding that M2-like macrophages increased levels of SULF1 and HSPG2 produced by fibroblasts, we examined SULF1 function in Wnt3A-mediated PCa tumoroid growth in tricultures. Comparing control or SULF1 knockout fibroblastic cells, we showed that SULF1 reduces Wnt3A-driven growth, cellularity, and cluster number of PCa cells in our 3D model. We conclude that SULF1 can suppress Wnt3A-driven growth signals in the desmoplastic stroma of PCa bone metastases, and SULF1 loss favors PCa progression, even in the presence of pro-tumorigenic TAMs.February 26, 2020 1/21 87 measurement is not possible. Instead, we quantified the transcript levels we detected in 88 each cell population using Imaris software, as described in Materials and Methods. 89Quantification of the SULF1 mRNA shows that approximately 95% of the signal is 90 confined to αSMA + activated fibroblasts, and is nearly undetected in E-cad + tumor 91 February 26, 2020 3/21

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Sulfatase-1 overexpression indicates poor prognosis in urothelial carcinoma of the urinary bladder and upper tract

Cited by 30 publications

References 42 publications

Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue

Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue

SULF1 suppresses Wnt3A-driven growth of bone metastatic prostate cancer in perlecan-modified 3D cancer-stroma-macrophage triculture models

SULF1 suppresses Wnt3A-driven growth of bone metastatic prostate cancer in perlecan-modified 3D cancer-stroma-macrophage triculture models

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