Expression of endothelial cell-specific molecule-1 regulated by hypoxia inducible factor-1α in human colon carcinoma: Impact of ESM-1 on prognosis and its correlation with clinicopathological features

Kim,Joo  Heon; Park,Mee  Young; Kim,Chang Nam; Kim,Kyo  Hyun; Kang,Ho  Bum; Kim,Kwang  Dong; Kim,Jae  Wha

doi:10.3892/or.2012.2012

Expression of endothelial cell-specific molecule-1 regulated by hypoxia inducible factor-1α in human colon carcinoma: Impact of ESM-1 on prognosis and its correlation with clinicopathological features

Authors:
- Joo Heon Kim
- Mee Young Park
- Chang Nam Kim
- Kyo Hyun Kim
- Ho Bum Kang
- Kwang Dong Kim
- Jae Wha Kim
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Affiliations: Department of Pathology, Eulji University School of Medicine, Daejeon 301‑070, Republic of Korea, Department of Surgery a, Eulji University School of Medicine, Daejeon 301‑070, Republic of Korea, Department of Preventive Medicine, Eulji University School of Medicine, Daejeon 301‑070, Republic of Korea, Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea, Division of Applied Life Science (BK21), PMBBRC, Gyeongsang National University, Jinju 660-701, Republic of Korea
Published online on: September 3, 2012 https://doi.org/10.3892/or.2012.2012
Pages: 1701-1708

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Abstract

Based on a previous finding that endothelial cell-specific molecule-1 (ESM-1) is a potential serum marker for colorectal cancer (CRC), the aim of this study was to clarify the clinicopathological significance of ESM-1 expression in CRC, and to explore the correlation between ESM-1 and HIF-1α in the tumorigenesis of CRC related to hypoxic conditions. ESM-1 mRNA expression was examined in CRC and corresponding normal mucosal tissues by reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR. This experiment confirmed that ESM-1 levels were high in CRC. We screened the tissue samples of 143 CRC patients. By immunohistochemistry, we determined that the ESM-1 immunoreactivity was significantly correlated with the tumor size, depth of invasion, nodal status, distant metastasis and Dukes' stage, and was an independent prognostic factor for disease recurrence and worse survival outcome (P=0.001). The modulation of ESM-1 under hypoxia was investigated, and it was confirmed that ESM-1 expression was induced by HIF1-α and significantly attenuated by small interfering RNA (siRNA) targeting HIF-1α in CRC cells. These results showed that ESM-1 is significantly overexpressed, which is regulated by HIF-1α in CRC patients, and can be used as a potential biomarker and a therapeutic target for CRC.

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1	Cannito S, Novo E, Compagnone A, et al: Redox mechanisms switch on hypoxia-dependent epithelial-mesenchymal transition in cancer cells. Carcinogenesis. 29:2267–2278. 2008. View Article : Google Scholar : PubMed/NCBI
2	Lluis JM, Buricchi F, Chiarugi P, Morales A and Fernandez-Checa JC: Dual role of mitochondrial reactive oxygen species in hypoxia signaling: activation of nuclear factor-{kappa}B via c-SRC and oxidant-dependent cell death. Cancer Res. 67:7368–7377. 2007.
3	Sansone P, Piazzi G, Paterini P, et al: Cyclooxygenase-2/carbonic anhydrase-IX up-regulation promotes invasive potential and hypoxia survival in colorectal cancer cells. J Cell Mol Med. 13:3876–3887. 2009. View Article : Google Scholar : PubMed/NCBI
4	To KK, Koshiji M, Hammer S and Huang LE: Genetic instability: the dark side of the hypoxic response. Cell Cycle. 4:881–882. 2005. View Article : Google Scholar : PubMed/NCBI
5	Huang LE, Bindra RS, Glazer PM and Harris AL: Hypoxia-induced genetic instability - a calculated mechanism underlying tumor progression. J Mol Med. 85:139–148. 2007. View Article : Google Scholar : PubMed/NCBI
6	Bristow RG and Hill RP: Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability. Nat Rev Cancer. 8:180–192. 2008. View Article : Google Scholar : PubMed/NCBI
7	Yoo YG, Hayashi M, Christensen J and Huang LE: An essential role of the HIF-1alpha-c-Myc axis in malignant progression. Ann NY Acad Sci. 1177:198–204. 2009. View Article : Google Scholar : PubMed/NCBI
8	Huang LE, Arany Z, Livingston DM and Bunn HF: Activation of hypoxia-inducible transcription factor depends primarily upon redox-sensitive stabilization of its alpha subunit. J Biol Chem. 271:32253–32259. 1996. View Article : Google Scholar
9	Maynard MA and Ohh M: The role of hypoxia-inducible factors in cancer. Cell Mol Life Sci. 64:2170–2180. 2007. View Article : Google Scholar : PubMed/NCBI
10	Harris AL: Hypoxia - a key regulatory factor in tumour growth. Nat Rev Cancer. 2:38–47. 2002. View Article : Google Scholar : PubMed/NCBI
11	Brahimi-Horn MC, Chiche J and Pouyssegur J: Hypoxia and cancer. J Mol Med. 85:1301–1307. 2007. View Article : Google Scholar
12	Brahimi-Horn MC and Pouyssegur J: Hypoxia in cancer cell metabolism and pH regulation. Essays Biochem. 43:165–178. 2007. View Article : Google Scholar : PubMed/NCBI
13	Brahimi-Horn MC, Chiche J and Pouyssegur J: Hypoxia signalling controls metabolic demand. Curr Opin Cell Biol. 19:223–229. 2007. View Article : Google Scholar : PubMed/NCBI
14	Brahimi-Horn MC and Pouyssegur J: HIF at a glance. J Cell Sci. 122:1055–1057. 2009. View Article : Google Scholar : PubMed/NCBI
15	Koukourakis MI, Giatromanolaki A, Simopoulos C, Polychronidis A and Sivridis E: Lactate dehydrogenase 5 (LDH5) relates to up-regulated hypoxia inducible factor pathway and metastasis in colorectal cancer. Clin Exp Metastasis. 22:25–30. 2005. View Article : Google Scholar : PubMed/NCBI
16	Sivridis E, Giatromanolaki A and Koukourakis MI: Proliferating fibroblasts at the invading tumour edge of colorectal adenocarcinomas are associated with endogenous markers of hypoxia, acidity, and oxidative stress. J Clin Pathol. 58:1033–1038. 2005. View Article : Google Scholar : PubMed/NCBI
17	Giles RH, Lolkema MP, Snijckers CM, et al: Interplay between VHL/HIF1alpha and Wnt/beta-catenin pathways during colorectal tumorigenesis. Oncogene. 25:3065–3070. 2006. View Article : Google Scholar : PubMed/NCBI
18	Koukourakis MI, Giatromanolaki A, Polychronidis A, et al: Endogenous markers of hypoxia/anaerobic metabolism and anemia in primary colorectal cancer. Cancer Sci. 97:582–588. 2006. View Article : Google Scholar : PubMed/NCBI
19	Lassalle P, Molet S, Janin A, et al: ESM-1 is a novel human endothelial cell-specific molecule expressed in lung and regulated by cytokines. J Biol Chem. 271:20458–20464. 1996. View Article : Google Scholar : PubMed/NCBI
20	Sarrazin S, Adam E, Lyon M, et al: Endocan or endothelial cell specific molecule-1 (ESM-1): a potential novel endothelial cell marker and a new target for cancer therapy. Biochim Biophys Acta. 1765:25–37. 2006.PubMed/NCBI
21	Bechard D, Scherpereel A, Hammad H, et al: Human endothelial-cell specific molecule-1 binds directly to the integrin CD11a/CD18 (LFA-1) and blocks binding to intercellular adhesion molecule-1. J Immunol. 167:3099–3106. 2001. View Article : Google Scholar : PubMed/NCBI
22	Bechard D, Meignin V, Scherpereel A, et al: Characterization of the secreted form of endothelial-cell-specific molecule 1 by specific monoclonal antibodies. J Vasc Res. 37:417–425. 2000. View Article : Google Scholar : PubMed/NCBI
23	Scherpereel A, Depontieu F, Grigoriu B, et al: Endocan, a new endothelial marker in human sepsis. Crit Care Med. 34:532–537. 2006. View Article : Google Scholar : PubMed/NCBI
24	Grigoriu BD, Depontieu F, Scherpereel A, et al: Endocan expression and relationship with survival in human non-small cell lung cancer. Clin Cancer Res. 12:4575–4582. 2006. View Article : Google Scholar : PubMed/NCBI
25	Abid MR, Yi X, Yano K, Shih SC and Aird WC: Vascular endocan is preferentially expressed in tumor endothelium. Microvasc Res. 72:136–145. 2006. View Article : Google Scholar : PubMed/NCBI
26	Leroy X, Aubert S, Zini L, et al: Vascular endocan (ESM-1) is markedly overexpressed in clear cell renal cell carcinoma. Histopathology. 56:180–187. 2010. View Article : Google Scholar : PubMed/NCBI
27	Aitkenhead M, Wang SJ, Nakatsu MN, Mestas J, Heard C and Hughes CC: Identification of endothelial cell genes expressed in an in vitro model of angiogenesis: induction of ESM-1, (beta)ig-h3, and NrCAM. Microvasc Res. 63:159–171. 2002. View Article : Google Scholar : PubMed/NCBI
28	Song Q, Jing H, Wu H, Zhou G, Kajiyama T and Kambara H: Gene expression analysis on a photodiode array-based bioluminescence analyzer by using sensitivity-improved SRPP. Analyst. 135:1315–1319. 2010. View Article : Google Scholar : PubMed/NCBI
29	Maurage CA, Adam E, Mineo JF, et al: Endocan expression and localization in human glioblastomas. J Neuropathol Exp Neurol. 68:633–641. 2009. View Article : Google Scholar : PubMed/NCBI
30	Kang YH, Ji NY, Lee CI, et al: ESM-1 silencing decreased cell survival, migration, and invasion and modulated cell cycle progression in hepatocellular carcinoma. Amino Acids. 40:1003–1013. 2010. View Article : Google Scholar : PubMed/NCBI
31	Ji NY, Kim YH, Jang YJ, et al: Identification of endothelial cell-specific molecule-1 as a potential serum marker for colorectal cancer. Cancer Sci. 101:2248–2253. 2010. View Article : Google Scholar : PubMed/NCBI
32	Semenza GL: Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 3:721–732. 2003. View Article : Google Scholar
33	Chen LY, Liu X, Wang SL and Qin CY: Over-expression of the endocan gene in endothelial cells from hepatocellular carcinoma is associated with angiogenesis and tumour invasion. J Int Med Res. 38:498–510. 2010. View Article : Google Scholar : PubMed/NCBI
34	Rennel E, Mellberg S, Dimberg A, et al: Endocan is a VEGF-A and PI3K regulated gene with increased expression in human renal cancer. Exp Cell Res. 313:1285–1294. 2007. View Article : Google Scholar : PubMed/NCBI
35	Bechard D, Gentina T, Delehedde M, et al: Endocan is a novel chondroitin sulfate/dermatan sulfate proteoglycan that promotes hepatocyte growth factor/scatter factor mitogenic activity. J Biol Chem. 276:48341–48349. 2001.
36	Chomczynski P and Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 162:156–159. 1987. View Article : Google Scholar : PubMed/NCBI
37	Hockel M and Vaupel P: Biological consequences of tumor hypoxia. Semin Oncol. 28:36–41. 2001. View Article : Google Scholar
38	Foo SS, Abbott DF, Lawrentschuk N and Scott AM: Functional imaging of intratumoral hypoxia. Mol Imaging Biol. 6:291–305. 2004. View Article : Google Scholar : PubMed/NCBI
39	Mabjeesh NJ and Amir S: Hypoxia-inducible factor (HIF) in human tumorigenesis. Histol Histopathol. 22:559–572. 2007.PubMed/NCBI
40	Filep JG: Endocan or endothelial cell-specific molecule-1: a novel prognostic marker of sepsis? Crit Care Med. 34:574–575. 2006. View Article : Google Scholar : PubMed/NCBI
41	Sarrazin S, Lyon M, Deakin JA, et al: Characterization and binding activity of the chondroitin/dermatan sulfate chain from endocan, a soluble endothelial proteoglycan. Glycobiology. 20:1380–1388. 2010. View Article : Google Scholar : PubMed/NCBI
42	Zuo L, Zhang SM, Hu RL, et al: Correlation between expression and differentiation of endocan in colorectal cancer. World J Gastroenterol. 14:4562–4568. 2008. View Article : Google Scholar : PubMed/NCBI
43	Ryan HE, Poloni M, McNulty W, et al: Hypoxia-inducible factor-1alpha is a positive factor in solid tumor growth. Cancer Res. 60:4010–4015. 2000.PubMed/NCBI
44	Swami M: Hypoxia: the HIF2alpha puzzle. Nat Rev Cancer. 10:6032010. View Article : Google Scholar : PubMed/NCBI
45	Gu YZ, Moran SM, Hogenesch JB, Wartman L and Bradfield CA: Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3alpha. Gene Expr. 7:205–213. 1998.PubMed/NCBI
46	Kietzmann T, Cornesse Y, Brechtel K, Modaressi S and Jungermann K: Perivenous expression of the mRNA of the three hypoxia-inducible factor alpha-subunits, HIF1alpha, HIF2alpha and HIF3alpha, in rat liver. Biochem J. 354:531–537. 2001. View Article : Google Scholar : PubMed/NCBI
47	Clottes E: Hypoxia-inducible factor 1: regulation, involvement in carcinogenesis and target for anticancer therapy. Bull Cancer. 92:119–127. 2005.(In French).
48	Zhong H, De Marzo AM, Laughner E, et al: Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res. 59:5830–5835. 1999.PubMed/NCBI
49	Baba Y, Nosho K, Shima K, et al: HIF1A overexpression is associated with poor prognosis in a cohort of 731 colorectal cancers. Am J Pathol. 176:2292–2301. 2010. View Article : Google Scholar : PubMed/NCBI