S100P, a calcium-binding protein, is preferentially associated with the growth of polypoid tumors in colorectal cancer

Chiang,Jy-Ming; Tan,Reping; Wang,Jen-Yi; Chen,Jinn-Shium; Lee,Yun-Shien; Hsieh,Pao-Shiu; Changchien,Chung  Rong; Chen,Jim-Ray

doi:10.3892/ijmm.2015.2065

S100P, a calcium-binding protein, is preferentially associated with the growth of polypoid tumors in colorectal cancer

Authors:
- Jy-Ming Chiang
- Reping Tan
- Jen-Yi Wang
- Jinn-Shium Chen
- Yun-Shien Lee
- Pao-Shiu Hsieh
- Chung Rong Changchien
- Jim-Ray Chen
View Affiliations

Affiliations: Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital at Linkou, Kwei-Shan, Tao-Yuan 333, Taiwan, R.O.C., Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital at Linkou, Kwei-Shan, Tao-Yuan 333, Taiwan, R.O.C., College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan, R.O.C.
Published online on: January 12, 2015 https://doi.org/10.3892/ijmm.2015.2065
Pages: 675-683
Copyright: © Chiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Colorectal cancer (CRC) is a genetically heterogeneous disease with distinct morphological patterns. It has been shown that polypoid and ulcerative CRC displays different genetic alterations. In the present study, we aimed to investigate genes with differential expression patterns between ulcerative and polypoid CRC. cDNA microarray analysis was performed to compare the gene expression profiles in samples of ulcerative and polypoid CRC with paired normal mucosa samples. Potential candidate genes were further validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot analysis and immunohistochemistry. The epigenetic regulation of gene expression was investigated using methylation-specific PCR (MSP). cDNA microarray analysis identified 11 upregulated and 14 downregulated genes which were differentially expressed in samples from both tumor types compared to the matched normal mucosa samples. Among these, S100P was the only upregulated gene preferentially associated with polypoid CRC (P=0.032). The samples of polypoid CRC displayed significantly higher S100P protein and mRNA expression levels than the samples of ulcerative CRC (P<0.05, respectively). Using semi-quantitative immunohistochemical analyses, S100P overexpression was found to be preferentially associated with polypoid CRC (24/30 vs. 14/40, P<0.001). The relative methylation level determined by MSP did not differ significantly between the samples of polypoid and ulcerative CRC (43.36 vs. 49.10%, P=0.168), indicating that promoter hypomethylation was not directly related to the upregulation of S100P mRNA. Our results demonstrate that the upregulation of S100P mRNA and protein expression is a predominant characteristic in polypoid CRC, whereas ulcerative CRC presents with a wide range of expression levels, indicating that S100P overexpression is not a key determinant in conferring invasion properties. The clinicopathological significance of S100P in CRC requires further investigation in well-controlled studies.

View Figures

View References

1	Fearon ER and Vogelstein B: A genetic model for colorectal tumorigenesis. Cell. 61:759–767. 1990. View Article : Google Scholar : PubMed/NCBI
2	Jass JR: Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology. 50:113–130. 2007. View Article : Google Scholar : PubMed/NCBI
3	Shimoda T, Ikegami M, Fujisaki J, Matsui T, Aizawa S and Ishikawa E: Early colorectal carcinoma with special reference to its development de novo. Cancer. 64:1138–1146. 1989. View Article : Google Scholar : PubMed/NCBI
4	Jass JR, Constable L, Sutherland R, Winterford C, Walsh MD, Young J and Leggett BA: Adenocarcinoma of colon differentiating as dome epithelium of gut-associated lymphoid tissue. Histopathology. 36:116–120. 2000. View Article : Google Scholar : PubMed/NCBI
5	Sedivy R, Wolf B, Kalipciyan M, Steger GG, Karner-Hanusch J and Mader RM: Genetic analysis of multiple synchronous lesions of the colon adenoma-carcinoma sequence. Br J Cancer. 82:1276–1282. 2000.
6	Yashiro M, Carethers JM, Laghi L, et al: Genetic pathways in the evolution of morphologically distinct colorectal neoplasms. Cancer Res. 61:2676–2683. 2001.PubMed/NCBI
7	Kaneko K, Fujii T, Kato S, et al: Growth patterns and genetic changes of colorectal carcinoma. Jpn J Clin Oncol. 28:196–201. 1998. View Article : Google Scholar : PubMed/NCBI
8	Uronis JM and Threadgill DW: Murine models of colorectal cancer. Mamm Genome. 20:261–268. 2009. View Article : Google Scholar : PubMed/NCBI
9	Richter H, Slezak P, Walch A, et al: Distinct chromosomal imbalances in nonpolypoid and polypoid colorectal adenomas indicate different genetic pathways in the development of colorectal neoplasms. Am J Pathol. 163:287–294. 2003. View Article : Google Scholar : PubMed/NCBI
10	van Wyk R, Slezak P, Hayes VM, et al: Somatic mutations of the APC, KRAS, and TP53 genes in nonpolypoid colorectal adenomas. Genes Chromosomes Cancer. 27:202–208. 2000. View Article : Google Scholar
11	Yamagata S, Muto T, Uchida Y, et al: Lower incidence of K-ras codon 12 mutation in flat colorectal adenomas than in polypoid adenomas. Jpn J Cancer Res. 85:147–151. 1994. View Article : Google Scholar : PubMed/NCBI
12	Chiang JM, Chou YH and Chou TB: K-ras codon 12 mutation determines the polypoid growth of colorectral cancer. Cancer Res. 58:3289–3293. 1998.PubMed/NCBI
13	Yamagata S, Muto T, Uchida Y, et al: Polypoid growth and K-ras codon 12 mutation in colorectal cancer. Cancer. 75:953–957. 1995. View Article : Google Scholar : PubMed/NCBI
14	Aust DE, Terdiman JP, Willenbucher RF, et al: Altered distribution of beta-catenin, and its binding proteins E-cadherin and APC, in ulcerative colitis-related colorectal cancers. Mod Pathol. 14:29–39. 2001. View Article : Google Scholar : PubMed/NCBI
15	Chiang JM, Chou YH, Chen TC, Ng KF and Lin JL: Nuclear beta-catenin expression is closely related to ulcerative growth of colorectal carcinoma. Br J Cancer. 86:1124–1129. 2002. View Article : Google Scholar : PubMed/NCBI
16	Trevino V, Falciani F and Barrera-Saldaña HA: DNA microarrays: a powerful genomic tool for biomedical and clinical research. Mol Med. 13:527–541. 2007. View Article : Google Scholar : PubMed/NCBI
17	Becker T, Gerke V, Kube E and Weber K: S100P, a novel Ca^2+-binding protein in human placenta. cDNA cloing, recombinant protein expression and Ca²⁺ binding properties. Eur J Biochem. 2007.541–547. 1992.
18	Wang TH, Lee YS, Chen ES, et al: Establishment of cDNA microarray analysis at the Genomic Medicine Research Core Laboratory (GMRCL) of Chang Gung Memorial Hospital. Chang Gung Med J. 27:243–260. 2004.PubMed/NCBI
19	Schneider CA, Rasband WS and Eliceiri KW: NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 9:671–675. 2012. View Article : Google Scholar : PubMed/NCBI
20	Herman JG, Graff JR, Myohanen S, Nelkin BD and Baylin SB: Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA. 93:9821–9826. 1996. View Article : Google Scholar : PubMed/NCBI
21	Bird A: DNA methylation patterns and epigenetic memory. Genes Dev. 16:6–21. 2002. View Article : Google Scholar : PubMed/NCBI
22	Sato N, Fukushima N, Matsubayashi H and Goggins M: Identification of maspin and S100P as novel hypomethylation targets in pancreatic cancer using global gene expression profiling. Oncogene. 23:1531–1538. 2004. View Article : Google Scholar : PubMed/NCBI
23	Chen JR, Chiang JM, Changchien CR, Chen JS, Tang RP and Wang JY: Mismatch repair protein expression in Amsterdam II criteria-positive patients in Taiwan. Br J Surg. 95:102–110. 2008. View Article : Google Scholar
24	Parkkila S, Pan PW, Ward A, et al: The calcium-binding protein S100P in normal and malignant human tissues. BMC Clin Pathol. 8(2): 2008
25	Lam FF, Jankova L, Dent OF, et al: Identification of distinctive protein expression patterns in colorectal adenoma. Proteomics. Clin Appl. 4:60–70. 2010. View Article : Google Scholar
26	Mousses S, Bubendorf L, Wagner U, et al: Clinical validation of candidate genes associated with prostate cancer progression in the CWR22 model system using tissue microarrays. Cancer Res. 62:1256–1260. 2002.PubMed/NCBI
27	Birkenkamp-Demtroder K, Olesen SH, Sorensen FB, et al: Differential gene expression in colon cancer of the caecum versus the sigmoid and rectosigmoid. Gut. 54:374–384. 2005. View Article : Google Scholar : PubMed/NCBI
28	Wang G, Platt-Higgins A, Carroll J, et al: Induction of metastasis by S100P in a rat mammary model and its association with poor survival of breast cancer patients. Cancer Res. 66:1199–1207. 2006. View Article : Google Scholar : PubMed/NCBI
29	Crnogorac-Jurcevic T, Missiaglia E, Blaveri E, et al: Molecular alterations in pancreatic carcinoma: expression profiling shows that dysregulated expression of S100 genes is highly prevalent. J Pathol. 201:63–74. 2003. View Article : Google Scholar : PubMed/NCBI
30	Rehbein G, Simm A, Hofmann HS, Silber RE and Bartling B: Molecular regulation of S100P in human lung adenocarcinomas. Int J Mol Med. 22:69–77. 2008.PubMed/NCBI
31	Guerreiro Da, Silva ID, Hu YF, Russo IH, et al: S100P calcium-binding protein overexpression is associated with immortalization of human breast epithelial cells in vitro and early stages of breast cancer development in vivo. Int J Oncol. 16:231–240. 2000.
32	Kita H, Hikichi Y, Hikami K, et al: Differential gene expression between flat adenoma and normal mucosa in the colon in a microarray analysis. J Gastroenterol. 41:1053–1063. 2006. View Article : Google Scholar : PubMed/NCBI
33	Fuentes MK, Nigavekar SS, Arumugam T, et al: RAGE activation by S100P in colon cancer stimulates growth, migration, and cell signaling pathways. Dis Colon Rectum. 50:1230–1240. 2007. View Article : Google Scholar : PubMed/NCBI
34	Jiang L, Lai YK, Zhang J, et al: Targeting S100P inhibits colon cancer growth and metastasis by Lentivirus-mediated RNA interference and proteomic analysis. Mol Med. 17:709–716. 2011. View Article : Google Scholar : PubMed/NCBI
35	Lao VV and Grady WM: Epigenetics and colorectal cancer. Nat Rev Gastroenterol Hepatol. 8:686–700. 2011. View Article : Google Scholar : PubMed/NCBI
36	Wang Q, Williamson M, Bott S, et al: Hypomethylation of WNT5A, CRIP1 and S100P in prostate cancer. Oncogene. 26:6560–6565. 2007. View Article : Google Scholar : PubMed/NCBI
37	Chandramouli A, Mercado-Pimentel ME, Hutchinson A, et al: The induction of S100p expression by the Prostaglandin E₂(PGE₂)/EP4 receptor signaling pathway in colon cancer cells. Cancer Biol Ther. 10:1056–1066. 2010. View Article : Google Scholar : PubMed/NCBI
38	Gibadulinova A, Tothova V, Pastorek J and Pastorekova S: Transcriptional regulation and functional implication of S100P in cancer. Amino Acids. 41:885–892. 2011. View Article : Google Scholar
39	Maletzki C, Bodammer P, Breitruck A and Kerkhoff C: S100 proteins as diagnostic and prognostic markers in colorectal and hepatocellular carcinoma. Hepat Mon. 12:e72402012.PubMed/NCBI
40	Arumugam T, Simeone DM, Schmidt AM and Logsdon CD: S100P stimulates cell proliferation and survival via receptor for activated glycation end products (RAGE). J Biol Chem. 279:5059–5065. 2004. View Article : Google Scholar
41	Zhuang L, Peng JB, Tou L, et al: Calcium-selective ion channel, CaT1, is apically localized in gastrointestinal tract epithelia and is aberrantly expressed in human malignancies. Lab Invest. 82:1755–1764. 2002. View Article : Google Scholar : PubMed/NCBI
42	Walther A, Johnstone E, Swanton C, Midgley R, Tomlinson I and Kerr D: Genetic prognostic and predictive markers in colorectal cancer. Nat Rev Cancer. 9:489–499. 2009. View Article : Google Scholar : PubMed/NCBI