Overexpression of heparan sulfate 6‑O‑sulfotransferase‑2 in colorectal cancer

Hatabe,Shigeru; Kimura,Hideharu; Arao,Tokuzo; Kato,Hiroaki; Hayashi,Hidetoshi; Nagai,Tomoyuki; Matsumoto,Kazuko; De Velasco,Marco; Fujita,Yoshihiko; Yamanouchi,Go; Fukushima,Masao; Yamada,Yasuhide; Ito,Akihiko; Okuno,Kiyotaka; Nishio,Kazuto

doi:10.3892/mco.2013.151

September-October 2013 Volume 1 Issue 5

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

September-October 2013 Volume 1 Issue 5

Full Size Image

Article

Overexpression of heparan sulfate 6‑O‑sulfotransferase‑2 in colorectal cancer

Authors:
- Shigeru Hatabe
- Hideharu Kimura
- Tokuzo Arao
- Hiroaki Kato
- Hidetoshi Hayashi
- Tomoyuki Nagai
- Kazuko Matsumoto
- Marco De Velasco
- Yoshihiko Fujita
- Go Yamanouchi
- Masao Fukushima
- Yasuhide Yamada
- Akihiko Ito
- Kiyotaka Okuno
- Kazuto Nishio
View Affiliations / Copyright

Affiliations: Department of Surgery, Kinki University School of Medicine, Osaka‑Sayama, Osaka 589‑8511, Japan, Department of Genome Biology, Kinki University School of Medicine, Osaka‑Sayama, Osaka 589‑8511, Japan, Sumitomo Bakelite Co., Ltd., Nishi‑ku, Kobe 651‑2241, Japan, Department of Medical Oncology, National Cancer Center Hospital, Chuo‑ku, Tokyo 104‑0045, Japan, Department of Pathology, Kinki University School of Medicine, Osaka‑Sayama, Osaka 589‑8511, Japan
Pages: 845-850
|
Published online on: July 23, 2013

https://doi.org/10.3892/mco.2013.151
Expand metrics +

Abstract

The heparan sulfate sulfotransferase gene family catalyzes the transfer of sulfate groups to heparan sulfate and regulates various growth factor‑receptor signaling pathways. however, the involvement of this gene family in cancer biology has not been elucidated. It was demonstrated that the heparan sulfate D‑glucosaminyl 6‑O‑sulfotransferase‑2 (HS6ST2) gene is overexpressed in colorectal cancer (CRC) and its clinical significance in patients with CRC was investigated. The mRNA levels of HS6ST2 in clinical CRC samples and various cancer cell lines were assessed using a microarray analysis and quantitative RT‑PCR, respectively. An immunohistochemical (IHC) analysis of the HS6ST2 protein was performed using 102 surgical specimens of CRC. The correlations between the HS6ST2 expression status and clinicopathological characteristics were then evaluated. HS6ST2 mRNA was significantly overexpressed by 37‑fold in CRC samples compared to paired colonic mucosa. High levels of HS6ST2 mRNA expression were also observed in colorectal, esophageal and lung cancer cell lines. the IHC analysis demonstrated that HS6ST2 was expressed in the cytoplasmic region of CRC cells, but not in normal colonic mucosal cells. Positive staining for HS6ST2 was detected in 40 patients (39.2%). There was no significant association between the clinicopathological characteristics and HS6ST2 expression. However, positive staining for HS6ST2 was associated with a poor survival (P=0.074, log‑rank test). In conclusion, HS6ST2 was found to be overexpressed in CRC and its expression tended to be a poor prognostic factor, although the correlation was not significant. These findings indicate that HS6ST2 may be a novel cancer‑related marker that may provide insight into the glycobiology of CRC.

View Figures

View References

1	Siegel R, Ward E, Brawley O and Jemal A: Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 61:212–236. 2011. View Article : Google Scholar : PubMed/NCBI
2	Kaneda H, Arao T, Tanaka K, et al: FOXQ1 is overexpressed in colorectal cancer and enhances tumorigenicity and tumor growth. Cancer Res. 70:2053–2063. 2010. View Article : Google Scholar : PubMed/NCBI
3	Sasisekharan R, Shriver Z, Venkataraman G and Narayanasami U: Roles of heparan-sulphate glycosaminoglycans in cancer. Nat Rev Cancer. 2:521–528. 2002. View Article : Google Scholar : PubMed/NCBI
4	Sanderson RD: Heparan sulfate proteoglycans in invasion and metastasis. Semin Cell Dev Biol. 12:89–98. 2001. View Article : Google Scholar : PubMed/NCBI
5	Matsuda K, Maruyama H, Guo F, Kleeff J, Itakura J, Matsumoto Y, Lander AD, et al: Glypican-1 is overexpressed in human breast cancer and modulates the mitogenic effects of multiple heparin-binding growth factors in breast cancer cells. Cancer Res. 61:5562–5569. 2001.PubMed/NCBI
6	Conejo JR, Kleeff J, Koliopanos A, Matsuda K, Zhu ZW, Goecke H, et al: Syndecan-1 expression is up-regulated in pancreatic but not in other gastrointestinal cancers. Int J Cancer. 88:12–20. 2000. View Article : Google Scholar : PubMed/NCBI
7	Ashikari-Hada S, Habuchi H, Kariya Y, Itoh N, Reddi AH and Kimata K: Characterization of growth factor-binding structures in heparin/heparan sulfate using an octasaccharide library. J Biol Chem. 279:12346–12354. 2004. View Article : Google Scholar : PubMed/NCBI
8	Pye DA, Vives RR, Turnbull JE, Hyde P and Gallagher JT: HS oligosaccharides require 6-O-sulphation for promotion of basic fibroblast growth factor mitogenic activity. J Biol Chem. 273:22936–22942. 1998.PubMed/NCBI
9	Robinson CJ, Harmer NJ, Goodger SJ, Blundell TL and Gallagher JT: Cooperative dimerization of fibroblast growth factor 1 (FGF1) upon a single heparin saccharide may drive the formation of 2:2:1 FGF1.FGFR2c.heparin ternary complexes. J Biol Chem. 280:42274–42282. 2005. View Article : Google Scholar : PubMed/NCBI
10	Ai X, Do AT, Kusche-Gullberg M, Lindahl U, Lu K and Emerson CP Jr: Substrate specificity and domain functions of extracellular heparin sulfate 6-O-endosulfatases, QSulf1 and QSulf2. J Biol Chem. 281:4969–4976. 2006. View Article : Google Scholar : PubMed/NCBI
11	Labbé E, Lock L, Letamendia A, et al: Transcriptional cooperation between the transforming growth factor-beta and Wnt pathways in mammary and intestinal tumorigenesis. Cancer Res. 67:75–84. 2007.PubMed/NCBI
12	Backen AC, Cole CL, Lau SC, et al: Heparan sulphate synthetic and editing enzymes in ovarian cancer. Br J Cancer. 96:1544–1548. 2007. View Article : Google Scholar : PubMed/NCBI
13	Song K, Li Q, Peng YB, Li J, Ding K, et al: Silencing of hHS6ST2 inhibits progression of pancreatic cancer through inhibition of Notch signalling. Biochem J. 436:271–282. 2011. View Article : Google Scholar : PubMed/NCBI
14	Pollari S, Käkönen RS, Mohammad KS, et al: Heparin-like polysaccharides reduce osteolytic bone destruction and tumor growth in a mouse model of breast cancer bone metastasis. Mol Cancer Res. 10:597–604. 2012. View Article : Google Scholar : PubMed/NCBI
15	Esko JD and Selleck SB: Order out of chaos: assembly of ligand binding sites in heparan sulfate. Annu Rev Biochem. 71:435–471. 2002. View Article : Google Scholar : PubMed/NCBI
16	Persimmon N and Bernfield M: Specificities of heparan sulfate proteoglycans in developmental processes. Nature. 404:725–728. 2000. View Article : Google Scholar
17	Nakato H and Kimata K: Heparan sulfate fine structure and specificity of proteoglycan functions. Biochem Biopsy Acta. 1573:312–318. 2002. View Article : Google Scholar : PubMed/NCBI
18	Chen E, Stringer SE, Rusch MA, Selleck SB and Ekker SC: A unique role for 6-O sulfation modification in zebrafish vascular development. Dev Biol. 284:364–376. 2005.
19	Lundin L, Larsson H, Kreuger J, Kanda S, Lindahl U, Salmivirta M and Claesson-Welsh L: Selectively desulfated heparin inhibits fibroblast growth factor-induced mitogenicity and angiogenesis. J Biol Chem. 275:24653–24660. 2000. View Article : Google Scholar : PubMed/NCBI
20	Nagai N, Habuchi H, Esko JD and Kimata K: Stem domains of heparan sulfate 6-O-sulfotransferase are required for Golgi localization, oligomer formation and enzyme activity. J Cell Sci. 117:3331–3341. 2004.PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Overexpression of heparan sulfate 6‑O‑sulfotransferase‑2 in colorectal cancer

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Related Articles