Cancer Res Treat.  2009 Mar;41(1):29-35.

Osteopontin, CD44, and NFkappaB Expression in Gastric Adenocarcinoma

Affiliations
  • 1Department of Pathology, Inje University Sanggye Paik Hospital, Seoul, Korea. pck2973@yahoo.co.kr
  • 2Department of Surgery, Inje University Sanggye Paik Hospital, Seoul, Korea.
  • 3Kyung Hee University East-West Neomedical Center Bone & Joint Research Center, Seoul, Korea.

Abstract

PURPOSE: Osteopontin (OPN) binds to CD44 and nuclear factor-kappaB (NFkappaB) and OPN mediates tumorigenesis, invasion and metastasis, but the interrelationships between OPN, CD44 and NFkappaB are not fully understood, and especially in gastric carcinogenesis. We examined the expressions of OPN, CD44, and NFkappaB in untreated gastric adenocarcinomas.
MATERIALS AND METHODS
The materials from 211 cases of gastric adenocarcinoma were immunostained for OPN, CD44 and NFkappaB by using a tissue microarray. The OPN mRNA expression was measured in 10 cases by performing real-time RT-PCR.
RESULTS
The expression of OPN, CD44 and NFkappaB was noted in 61.7%, 11.4% and 26.6% of the adenocarcinoma tissues, respectively. No significant correlation was detected among the expressions of these proteins. The OPN protein expression was negatively correlated with angioinvasion (p<0.05) and patient survival (p<0.05), whereas the CD44 and NFkappaB protein expressions were not correlated with any of the clinicopathological factors we examined. The depth of invasion, lymph node status and perineural invasions were prognostic factors based on the Cox analysis. The OPN mRNA expression showed no significant difference between the adenocarcinoma and the paired normal mucosa on real-time RT-PCR.
CONCLUSION
OPN may have a currently undetermined role in gastric carcinogenesis, and CD44 and NFkappaB may have minor roles in gastric adenocarcinoma.

Keyword

Stomach; Adenocarcinoma; Osteopontin; CD44; NFkappaB

MeSH Terms

Adenocarcinoma
Cell Transformation, Neoplastic
Humans
Lymph Nodes
Mucous Membrane
Neoplasm Metastasis
Osteopontin
Proteins
RNA, Messenger
Stomach
Osteopontin
Proteins
RNA, Messenger

Figure

  • Fig. 1 The expression of OPN, CD44 and NFκB proteins in gastric adenocarcinoma tissue [A, H&E (×100); B, OPN (×200); C, CD44 (×200); D, NFκB (×200)].

  • Fig. 2 On the survival analysis, the OPN (A) protein expression was negatively correlated with patient survival, but the CD44 (B) and NFκB (C) protein expressions in advanced gastric cancer were not related to patient survival [ (+), positive expression; (-), negative expression].


Reference

1. Fock KM, Talley N, Moayyedi P, Hunt R, Azuma T, Sugano K, et al. Asia-Pacific consensus guidelines on gastric cancer prevention. J Gastroenterol Hepatol. 2008; 23:351–365. PMID: 18318820.
Article
2. Yasui W, Sentani K, Motoshita J, Nakayama H. Molecular pathobiology of gastric cancer. Scand J Surg. 2006; 95:225–231. PMID: 17249269.
Article
3. Guarino V, Faviana P, Salvatore G, Castellone MD, Cirafici AM, De Falco V, et al. Osteopontin is overexpressed in human papillary thyroid carcinomas and enhances thyroid carcinoma cell invasiveness. J Clin Endocrinol Metab. 2005; 90:5270–5278. PMID: 15998773.
Article
4. Cook AC, Tuck AB, McCarthy S, Turner JG, Irby RB, Bloom GC, et al. Osteopontin induces multiple changes in gene expression that reflect the six 'hallmarks of cancer' in a model of breast cancer progression. Mol Carcinog. 2005; 43:225–236. PMID: 15864800.
Article
5. Irby RB, McCarthy SM, Yeatman TJ. Osteopontin regulates multiple functions contributing to human colon cancer development and progression. Clin Exp Metastasis. 2004; 21:515–523. PMID: 15679049.
Article
6. Tuck AB, Hota C, Wilson SM, Chambers AF. Osteopontin-induced migration of human mammary epithelial cells involves activation of EGF receptor and multiple signal transduction pathways. Oncogene. 2003; 22:1198–1205. PMID: 12606946.
Article
7. Tuck AB, Chambers AF. The role of osteopontin in breast cancer: clinical and experimental studies. J Mammary Gland Biol Neoplasia. 2001; 6:419–429. PMID: 12013531.
8. Murai T, Miyazaki Y, Nishinakamura H, Sugahara KN, Miyauchi T, Sako Y, et al. Engagement of CD44 promotes Rac activation and CD44 cleavage during tumor cell migration. J Biol Chem. 2004; 279:4541–4550. PMID: 14623895.
Article
9. Philip S, Kundu GC. Osteopontin induces nuclear factor κB-mediated promatrix metalloproteinase-2 activation through IκBα/IKK signaling pathways, and curcumin (diferulolylmethane) down-regulates these pathways. J Biol Chem. 2003; 278:14487–14497. PMID: 12473670.
10. Philip S, Bulbule A, Kundu GC. Osteopontin stimulates tumor growth and activation of promatrix metalloproteinases-2 through nuclear factor-kappa B-mediated induction of membrane type 1 matrix metalloproteinase in murine melanoma cells. J Biol Chem. 2001; 276:44926–44935. PMID: 11564733.
11. Renault MA, Jalvy S, Potier M, Belloc I, Genot E, Dekker LV, et al. UTP induces osteopontin expression through a coordinate action of NFkB, activator protein-1, and upstream stimulatory factor in arterial smooth muscle cells. J Biol Chem. 2005; 280:2708–2713. PMID: 15557322.
12. Samant RS, Clark DW, Fillmore RA, Cicek M, Metge BJ, Chandramouli KH, et al. Breast cancer metastasis suppressor 1 (BRMS1) inhibits osteopontin transcription by abrogating NFkB activation. Mol Cancer. 2007; 6:6–15. PMID: 17227585.
Article
13. Kim JY, Lim S, Park K. Cyclooxygenase-2 and c-erbB-2 expression in gastric carcinoma assessed using tissue microarrays. Appl Immunohistochem Mol Morphol. 2004; 12:67–70. PMID: 15163022.
14. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods. 2001; 25:402–408. PMID: 11846609.
15. Weber GF. The metastasis gene osteopontin: a candidate target for cancer therapy. Biochem Biophys Acta. 2001; 1552:61–85. PMID: 11825687.
Article
16. Eschrich S, Yang I, Bloom G, Kwong KY, Boulware D, Cantor A, et al. Molecular staging for survival prediction of gastric cancer patients. J Clin Oncol. 2005; 23:3526–3535. PMID: 15908663.
17. Wu CY, Wu MS, Chiang EP, Wu CC, Chen YJ, Chen CJ, et al. Elevated plasma osteopontin associated with gastric cancer development, invasion and survival. Gut. 2007; 56:782–789. PMID: 17148500.
Article
18. Coppola D, Szabo M, Boulware D, Muraca P, Alsarraj M, Chambers AF, et al. Correlation of osteopontin protein expression and pathological stage across a side variety of tumor histologies. Clin Cancer Res. 2004; 10:184–190. PMID: 14734468.
19. Selkirk SM, Morrow J, Barone TA, Hoffer A, Lock J, DeChant A, et al. Elevation of osteopontin levels in brain tumor cells reduces burden and promotes survival through the inhibition of cell dispersal. J Neurooncol. 2008; 86:285–296. PMID: 17928956.
Article
20. Matsuzaki H, Shima K, Muramatsu T, Ro Y, Hashimoto S, Shibahara T, et al. Osteopontin as biomarker in early invasion by squamous cell carcinoma in tongue. J Oral Pathol Med. 2007; 36:30–34. PMID: 17181739.
Article
21. Lee JL, Wang MJ, Sudhir PR, Chen GD, Chi CW, Chen JY. Osteopontin promotes integrin activation through outside-in and inside-out mechanism:OPN-CD44v interaction enhances survival in gastrointestinal cancer cells. Cancer Res. 2007; 67:2089–2097. PMID: 17332338.
22. Wai PY, Mi Z, Guo H, Sarraf-Yazdi S, Gao C, Wei J, et al. Osteopontin silencing by small interfering RNA suppresses in vitro and in vivo CT26 murine colon adenocarcinoma metastasis. Carcinogenesis. 2005; 26:741–751. PMID: 15661802.
Article
23. Bourguignon LY, Xia W, Wong G. Hyaluronan-mediated CD44 interaction with p300 and SIRT1 regulates beta-catenin signaling and NFkB-specific transcription activity leading to MDR1 and Bcl-xL gene expression and chemoresistance in breast tumor cells. J Biol Chem. 2009; 284:2657–2671. PMID: 19047049.
24. Orian-Rousseau V, Chen L, Sleeman JP, Herrlich P, Ponta H. CD44 is required for two consecutive steps in HGF/c-Met signaling. Genes Dev. 2002; 16:3074–3086. PMID: 12464636.
Article
Full Text Links
  • CRT
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr