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Bin Yi, Yinghe Qiu, Weidan Ji, Miaoyan Wei, Chunying Liu, Zhangxiao Peng, Yongjie Zhang, Zhiwei Quan, Zhaohui Tang, Changqing Su
Cell surface heparan sulfate proteoglycan (HSPG) is a group of critical glycoproteins that mediates signal transduction. Sulfated HSPG can mediate the activation of a variety of cell growth factor signal pathway to promote the progression of gallbladder carcinoma (GBC). This study analyzed 527 clinical GBC specimens and confirmed that the HSPG sulfation level was significantly higher in GBC tissues than in gallbladder mucosa (GBM) tissues. The high HSPG sulfation level was closely associated with poor differentiation, local metastasis, and advanced clinical stage of GBC; it was also associated with the shortening of disease-free survival (DFS) and overall survival (OS) and influenced the outcome of chemotherapy or radio-chemotherapy in patients with GBC recurrence...
October 28, 2016: Cancer Letters
A S Laganà, F Colonese, E Colonese, V Sofo, F M Salmeri, R Granese, B Chiofalo, L Ciancimino, O Triolo
Ovarian cancer is one of the most frequent solid tumor that shows clearly biphasic behaviour in response to chemotherapy, with the majority of patients who achieved complete remission after the first cycle of chemotherapy, and subsequently present a relapse which, in most cases, leads to death. Epithelial ovarian cancer (EOC) arises as a consequence of genetic alterations that affect the cells of the ovarian surface, which leads to changes that occur through the activation of oncogenes and inactivation of tumor suppressor genes...
2015: European Journal of Gynaecological Oncology
Susmita Mondal, Debarshi Roy, Juliana Camacho-Pereira, Ashwani Khurana, Eduardo Chini, Lifeng Yang, Joelle Baddour, Katherine Stilles, Seth Padmabandu, Sam Leung, Steve Kalloger, Blake Gilks, Val Lowe, Thomas Dierks, Edward Hammond, Keith Dredge, Deepak Nagrath, Viji Shridhar
Warburg effect has emerged as a potential hallmark of many cancers. However, the molecular mechanisms that led to this metabolic state of aerobic glycolysis, particularly in ovarian cancer (OVCA) have not been completely elucidated. HSulf-1 predominantly functions by limiting the bioavailability of heparan binding growth factors and hence their downstream signaling. Here we report that HSulf-1, a known putative tumor suppressor, is a negative regulator of glycolysis. Silencing of HSulf-1 expression in OV202 cell line increased glucose uptake and lactate production by upregulating glycolytic genes such as Glut1, HKII, LDHA, as well as metabolites...
October 20, 2015: Oncotarget
Kaori Kuwabara, Kazuchika Nishitsuji, Kenji Uchimura, Shang-Cheng Hung, Makoto Mizuguchi, Hiroyuki Nakajima, Shiho Mikawa, Norihiro Kobayashi, Hiroyuki Saito, Naomi Sakashita
The single amino acid mutation G26R in human apolipoprotein A-I (apoA-I) is associated with familial amyloid polyneuropathy III. ApoA-I carrying this mutation (apoA-IIowa) forms amyloid fibrils in vitro. Heparan sulfate (HS) is a glycosaminoglycan that is abundant at the cell surface and in the extracellular matrix. Although HS and its highly sulfated domains are involved in aggregation of amyloid-β and accumulate in cerebral amyloid plaques of patients with Alzheimer disease and mouse models of this disease, the role of HS in familial amyloid polyneuropathy III has never been addressed...
October 2, 2015: Journal of Biological Chemistry
Debarshi Roy, Susmita Mondal, Chen Wang, Xiaoping He, Ashwani Khurana, Shailendra Giri, Robert Hoffmann, Deok-Beom Jung, Sung H Kim, Eduardo N Chini, Juliana Camacho Periera, Clifford D Folmes, Andrea Mariani, Sean C Dowdy, Jamie N Bakkum-Gamez, Shaun M Riska, Ann L Oberg, Edward D Karoly, Lauren N Bell, Jeremy Chien, Viji Shridhar
[This corrects the article DOI: 10.1186/2049-3002-2-13.].
2014: Cancer & Metabolism
Xiao-Ping Yang, Ling Liu, Ping Wang, Sheng-Lin Ma
BACKGROUND: Human sulfatase-1 (Hsulf-1) is an endosulfatase that selectively removes sulfate groups from heparan sulfate proteoglycans (HSPGs), altering the binding of several growth factors and cytokines to HSPG to regulate cell proliferation, cell motility, and apoptosis. We investigated the role of combined cancer gene therapy with Hsulf-1 and cytosine deaminase/5-fluorocytosine (CD/5-FC) suicide gene on a hepatocellular carcinoma (HCC) cell line, HepG2, in vitro and in vivo. METHODS: Reverse transcription polymerase chain reaction and immunohistochemistry were used to determine the expression of Hsulf-1 in HCC...
May 20, 2015: Chinese Medical Journal
Carolina M Vicente, Marcelo A Lima, Helena B Nader, Leny Toma
BACKGROUND: SULF2 is a 6-O-endosulfatase which removes 6-O sulfate residues from N-glucosamine present on heparan sulfate (HS). The sulfation pattern of HS influences signaling events mediated by heparan sulfate proteoglycans (HSPGs) located on cell surface, which are critical for the interactions with growth factors and their receptors. Alterations in SULF2 expression have been identified in the context of several cancer types but its function in cancer is still unclear where the precise molecular mechanism involved has not been fully deciphered...
2015: Journal of Experimental & Clinical Cancer Research: CR
Kenji Uchimura
Sulf-1 and Sulf-2 are endo-acting extracellular sulfatases. The Sulfs liberate 6-O sulfate groups, mainly from N, 6-O, and 2-O trisulfated disaccharides of heparan sulfate (HS)/heparin chains. The Sulfs have been shown to modulate the interaction of a number of protein ligands including growth factors and morphogens with HS/heparin and thus regulate the signaling of these ligands. They also play important roles in development and are dysregulated in many cancers. The establishment of the expression of the Sulfs and methods of assaying them has been desirable to investigate these enzymes...
2015: Methods in Molecular Biology
Debarshi Roy, Susmita Mondal, Chen Wang, Xiaoping He, Ashwani Khurana, Shailendra Giri, Robert Hoffmann, Deok-Beom Jung, Sung H Kim, Eduardo N Chini, Juliana Camacho Periera, Clifford D Folmes, Andrea Mariani, Sean C Dowdy, Jamie N Bakkum-Gamez, Shaun M Riska, Ann L Oberg, Edward D Karoly, Lauren N Bell, Jeremy Chien, Viji Shridhar
BACKGROUND: Loss of the endosulfatase HSulf-1 is common in ovarian cancer, upregulates heparin binding growth factor signaling and potentiates tumorigenesis and angiogenesis. However, metabolic differences between isogenic cells with and without HSulf-1 have not been characterized upon HSulf-1 suppression in vitro. Since growth factor signaling is closely tied to metabolic alterations, we determined the extent to which HSulf-1 loss affects cancer cell metabolism. RESULTS: Ingenuity pathway analysis of gene expression in HSulf-1 shRNA-silenced cells (Sh1 and Sh2 cells) compared to non-targeted control shRNA cells (NTC cells) and subsequent Kyoto Encyclopedia of Genes and Genomics (KEGG) database analysis showed altered metabolic pathways with changes in the lipid metabolism as one of the major pathways altered inSh1 and 2 cells...
2014: Cancer & Metabolism
Yu Huang, Yang Mao, Jo Ann Buczek-Thomas, Matthew A Nugent, Joseph Zaia
Sulfs are extracellular endosulfatases that selectively remove the 6-O-sulfate groups from cell surface heparan sulfate (HS) chain. By altering the sulfation at these particular sites, Sulfs function to remodel HS chains. As a result of the remodeling activity, HSulf2 regulates a multitude of cell-signaling events that depend on interactions between proteins and HS. Previous efforts to characterize the substrate specificity of human Sulfs (HSulfs) focused on the analysis of HS disaccharides and synthetic repeating units...
2014: PloS One
Mitsutaka Nishida, Kazuma Murata, Yoshihiro Kanamaru, Tomio Yabe
Although previous reports have suggested that pectin induces morphological changes of the small intestine in vivo, the molecular mechanisms have not been elucidated. As heparan sulfate plays important roles in development of the small intestine, to verify the involvement of heparan sulfate (HS) in the pectin-induced morphological changes of the small intestine, the effects of pectin from Prunus domestica L. on cell-surface HS were investigated using differentiated Caco-2 cells. Disaccharide compositional analysis revealed that sulfated structures of HS were markedly changed by pectin administration...
2014: Bioscience, Biotechnology, and Biochemistry
Gaoya Xu, Weidan Ji, Yinghan Su, Yang Xu, Yan Yan, Shuwen Shen, Xiaoya Li, Bin Sun, Haihua Qian, Lei Chen, Xiaohui Fu, Mengchao Wu, Changqing Su
The human sulfatase 1 (hSulf-1) gene encodes an endosulfatase that functions to inhibit the heparin-binding growth factor signaling, including the basic fibroblast growth factor (bFGF)-mediated pathway, by desulfating the cell surface heparan sulfate proteoglycans (HSPGs). bFGF could stimulate cell cycle progression and inhibit cell apoptosis, this biological effect can be reversed by hSulf-1. However, molecular mechanisms have not been fully reported. In the current study, by reactivation of hSulf-1 expression and function in the hSulf-1-negative hepatocellular carcinoma (HCC) cell lines and HCC xenograft tumors, we found that hSulf-1 blocked the bFGF effect on the promotion of cell cycle and inhibition of apoptosis...
July 15, 2014: Oncotarget
Ling Liu, Feng Ding, Jiwei Chen, Boyong Wang, Zhisu Liu
Human sulfatase-1 (hSulf-1) has been shown to desulfate cellular heparin sulfate proteoglycans and modulate several growth factors and cytokines. However, hSulf-1 has not been previously shown to mediate the signal transducer and activator of transcription 3 (stat3) signaling pathway, which is known to regulate cell proliferation, motility and apoptosis. The present study investigated the role of hSulf-1 in stat3 signaling in hepatocellular cancer. hSulf-1 expression vector and stat3 small interfering RNA (siRNA) were constructed to control the expression of hSulf-1 and stat3 in HepG2 cells...
April 2014: Oncology Letters
Xiaoping He, Ashwani Khurana, Debarshi Roy, Scott Kaufmann, Viji Shridhar
The expression of human Sulfatase1 (HSulf-1) is downregulated in the majority of primary ovarian cancer tumors, but the functional consequence of this downregulation remains unclear. Using two different shRNAs (Sh1 and Sh2), HSulf-1 expression was stably downregulated in ovarian cancer OV202 cells. We found that HSulf-1-deficient OV202 Sh1 and Sh2 cells formed colonies in soft agar. In contrast, nontargeting control (NTC) shRNA-transduced OV202 cells did not form any colonies. Moreover, subcutaneous injection of OV202 HSulf-1-deficient cells resulted in tumor formation in nude mice, whereas OV202 NTC cells did not...
October 15, 2014: International Journal of Cancer. Journal International du Cancer
Longlong Bao, Yan Yan, Can Xu, Weidan Ji, Shuwen Shen, Gaoya Xu, Yong Zeng, Bin Sun, Haihua Qian, Lei Chen, Mengchao Wu, Changqing Su, Jie Chen
MicroRNAs (miRNAs) have been believed to associate with malignant progression including cancer cell proliferation, apoptosis, differentiation, angiogenesis, invasion and metastasis. However, the functions of miRNAs are intricate, one miRNA can directly or indirectly target multiple genes and function as oncogene or tumor suppressor gene. In this study, we found that miR-21 inhibits PTEN and human sulfatase-1 (hSulf-1) expression in hepatocellular carcinoma (HCC) cells. The hSulf-1 is a heparin-degrading endosulfatase, which can inhibit the heparin binding growth factor-mediated signaling transduction into cells...
September 1, 2013: Cancer Letters
Amal Seffouh, Fabian Milz, Cédric Przybylski, Cédric Laguri, Arie Oosterhof, Sébastien Bourcier, Rabia Sadir, Elodie Dutkowski, Régis Daniel, Toin H van Kuppevelt, Thomas Dierks, Hugues Lortat-Jacob, Romain R Vivès
Sulfs are extracellular sulfatases that have emerged recently as critical regulators of heparan sulfate (HS) activities through their ability to catalyze specific 6-O-desulfation of the polysaccharide. Consequently, Sulfs have been involved in many physiological and pathological processes, and notably for Sulf-2, in the development of cancers with poor prognosis. Despite growing interest, little is known about the structure and activity of these enzymes and the way they induce dynamic remodeling of HS 6-O-sulfation status...
June 2013: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Ashwani Khurana, Daniah Beleford, Xiaoping He, Jeremy Chien, Viji Shridhar
Endosulfatases HSulf-1 and -2 (also referred to as Sulf1 and -2) represent a family of enzymes that modulate heparin binding growth factor signaling. Heparan sulfatase 1 (HSulf-1) and heparan sulfatase 2 (HSulf-2) are two important 6-O endosulfatases which remove or edit 6-O sulfate residues of N-glucosamine present on highly sulfated HS. Alteration of heparan sulfatases have been identified in the context of several cancer types. Many cancer types either exhibit increased or decreased HSulfs expression at the transcript levels...
2013: American Journal of Cancer Research
Yan Zhang, Lin Fang, Quan'an Zhang, Qin Zheng, Jinlong Tong, Xiaohui Fu, Xiaoqing Jiang, Changqing Su, Junnian Zheng
Gene therapy and antibody approaches are crucial auxiliary strategies for hepatocellular carcinoma (HCC) treatment. Previously, we established a survivin promoter-regulated oncolytic adenovirus that has inhibitory effect on HCC growth. The human sulfatase-1 (hSulf-1) gene can suppress the growth factor signaling pathways, then inhibit the proliferation of cancer cells and enhance cellular sensitivity to radiotherapy and chemotherapy. I(131)-metuximab (I(131)-mab) is a monoclonal anti-HCC antibody that conjugated to I(131) and specifically recognizes the HAb18G/CD147 antigen on HCC cells...
June 2013: Molecular Oncology
Huiying Zhang, Donna R Newman, James C Bonner, Philip L Sannes
Environmental exposure to cadmium is known to cause damage to alveolar epithelial cells of the lung, impair their capacity to repair, and result in permanent structural alterations. Cell surface heparan sulfate proteoglycans (HSPGs) can modulate cell responses to injury through their interactions with soluble effector molecules. These interactions are often sulfate specific, and the removal of sulfate groups from HS side chains could be expected to influence cellular injury, such as that caused by exposure to cadmium...
November 15, 2012: Toxicology and Applied Pharmacology
Hu Liu, Xiaohui Fu, Weidan Ji, Kai Liu, Longlong Bao, Yan Yan, Mengchao Wu, Jiahe Yang, Changqing Su
AIM:   The human sulfatase-1 (hSulf-1) gene regulates the sulfation of heparan sulfate proteoglycans (HSPG) and suppresses tumorigenesis and angiogenesis by inhibiting several growth factor signaling pathways. Because the serine-threonine protein kinase (AKT) and extracellular signal-regulated kinase (ERK) signaling pathways are critical in cell survival, proliferation, migration and angiogenesis, the possible correlation between hSulf-1 and AKT/ERK signaling in hepatocellular carcinoma (HCC) cells needs further exploration...
May 2013: Hepatology Research: the Official Journal of the Japan Society of Hepatology
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