Osteopontin is a promoter for hepatocellular carcinoma metastasis: a summary of 10 years of studies

Lunxiu Qin

PDF(298 KB)
PDF(298 KB)
Front. Med. ›› 2014, Vol. 8 ›› Issue (1) : 24-32. DOI: 10.1007/s11684-014-0312-8
REVIEW

Osteopontin is a promoter for hepatocellular carcinoma metastasis: a summary of 10 years of studies

Author information +
History +

Abstract

In this review, we summarize the novel findings from our series of studies on the leading metastasis-related gene, osteopontin (OPN). In our previous gene expression profiling study, OPN was identified as one of the leading genes associated with the metastasis of hepatocellular carcinoma (HCC). We focused on OPN to evaluate its prognostic values and important roles in HCC metastasis. A retrospective study of large cohorts of HCC patients demonstrated that plasma OPN level was one of the leading independent prognostic factors for HCC patients, even in the early stage of HCC, and could serve as a surrogate serologic biomarker for monitoring the treatment response and tumor recurrence after HCC resection. Using both in vitro and in vivo investigations, we found that OPN has an important role in metastasis and tumor growth of HCC and is an attractive potential therapeutic target for combating HCC metastasis. We also found that OPN+ HCC cells have much more amplifications at chromosomal regions, and promoter polymorphisms are important in the regulation of OPN expression and tumor growth and lung metastasis of HCC.

Keywords

osteopontin (OPN) / hepatocellular carcinoma / metastasis / prognosis / therapeutic target / biomarker / genetic polymorphism

Cite this article

Download citation ▾
Lunxiu Qin. Osteopontin is a promoter for hepatocellular carcinoma metastasis: a summary of 10 years of studies. Front Med, 2014, 8(1): 24‒32 https://doi.org/10.1007/s11684-014-0312-8

References

[1]
McAllister SS, Gifford AM, Greiner AL, Kelleher SP, Saelzler MP, Ince TA, Reinhardt F, Harris LN, Hylander BL, Repasky EA, Weinberg RA. Systemic endocrine instigation of indolent tumor growth requires osteopontin. Cell2008; 133(6): 994-1005
CrossRef Pubmed Google scholar
[2]
Denhardt DT, Giachelli CM, Rittling SR. Role of osteopontin in cellular signaling and toxicant injury. Annu Rev Pharmacol Toxicol2001; 41(1): 723-749
CrossRef Pubmed Google scholar
[3]
Weber GF. The metastasis gene osteopontin: a candidate target for cancer therapy. Biochim Biophys Acta2001; 1552(2): 61-85
Pubmed
[4]
Wu CY, Wu MS, Chiang EP, Wu CC, Chen YJ, Chen CJ, Chi NH, Chen GH, Lin JT. Elevated plasma osteopontin associated with gastric cancer development, invasion and survival. Gut2007; 56(6): 782-789
CrossRef Pubmed Google scholar
[5]
Khodavirdi AC, Song Z, Yang S, Zhong C, Wang S, Wu H, Pritchard C, Nelson PS, Roy-Burman P. Increased expression of osteopontin contributes to the progression of prostate cancer. Cancer Res2006; 66(2): 883-888
CrossRef Pubmed Google scholar
[6]
Bramwell VH, Doig GS, Tuck AB, Wilson SM, Tonkin KS, Tomiak A, Perera F, Vandenberg TA, Chambers AF. Serial plasma osteopontin levels have prognostic value in metastatic breast cancer. Clin Cancer Res2006; 12(11): 3337-3343
CrossRef Pubmed Google scholar
[7]
Medico E, Gentile A, Lo Celso C, Williams TA, Gambarotta G, Trusolino L, Comoglio PM. Osteopontin is an autocrine mediator of hepatocyte growth factor-induced invasive growth. Cancer Res2001; 61(15): 5861-5868
Pubmed
[8]
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. Oncogene2003; 22(8): 1198-1205
CrossRef Pubmed Google scholar
[9]
Ariztia EV, Subbarao V, Solt DB, Rademaker AW, Iyer AP, Oltvai ZN. Osteopontin contributes to hepatocyte growth factor-induced tumor growth and metastasis formation. Exp Cell Res2003; 288(2): 257-267
CrossRef Pubmed Google scholar
[10]
Sharp JA, Sung V, Slavin J, Thompson EW, Henderson MA. Tumor cells are the source of osteopontin and bone sialoprotein expression in human breast cancer. Lab Invest1999; 79(7): 869-877
Pubmed
[11]
Urquidi V, Sloan D, Kawai K, Agarwal D, Woodman AC, Tarin D, Goodison S. Contrasting expression of thrombospondin-1 and osteopontin correlates with absence or presence of metastatic phenotype in an isogenic model of spontaneous human breast cancer metastasis. Clin Cancer Res2002; 8(1): 61-74
Pubmed
[12]
Chen H, Ke Y, Oates AJ, Barraclough R, Rudland PS. Isolation of and effector for metastasis-inducing DNAs from a human metastatic carcinoma cell line. Oncogene1997; 14(13): 1581-1588
CrossRef Pubmed Google scholar
[13]
Oates AJ, Barraclough R, Rudland PS. The identification of osteopontin as a metastasis-related gene product in a rodent mammary tumour model. Oncogene1996; 13(1): 97-104
Pubmed
[14]
Ye QH, Qin LX, Forgues M, He P, Kim JW, Peng AC, Simon R, Li Y, Robles AI, Chen Y, Ma ZC, Wu ZQ, Ye SL, Liu YK, Tang ZY, Wang XW. Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning. Nat Med2003; 9(4): 416-423
CrossRef Pubmed Google scholar
[15]
Zhang H, Ye QH, Ren N, Zhao L, Wang YF, Wu X, Sun HC, Wang L, Zhang BH, Liu YK, Tang ZY, Qin LX. The prognostic significance of preoperative plasma levels of osteopontin in patients with hepatocellular carcinoma. J Cancer Res Clin Oncol2006; 132(11): 709-717
CrossRef Pubmed Google scholar
[16]
Huang H, Zhang XF, Zhou HJ, Xue YH, Dong QZ, Ye QH, Qin LX. Expression and prognostic significance of osteopontin and caspase-3 in hepatocellular carcinoma patients after curative resection. Cancer Sci2010; 101(5): 1314-1319
CrossRef Pubmed Google scholar
[17]
Sun J, Xu HM, Zhou HJ, Dong QZ, Zhao Y, Fu LY, Hei ZY, Ye QH, Ren N, Jia HL, Qin LX. The prognostic significance of preoperative plasma levels of osteopontin in patients with TNM stage-I of hepatocellular carcinoma. J Cancer Res Clin Oncol2010; 136(1): 1-7
CrossRef Pubmed Google scholar
[18]
Zhou C, Zhou HJ, Zhang XF, Lou LL, Ye QH, Zheng Y, Wang J, Zhu HT, Dong QZ, Jia HL, Zhu WW, Guo L, Zhao Y, Gao DM, Qin LX. Postoperative serum osteopontin level is a novel monitor for treatment response and tumor recurrence after resection of hepatitis B-related hepatocellular carcinoma. Ann Surg Oncol2013; 20(3): 929-937
CrossRef Pubmed Google scholar
[19]
Sun BS, Dong QZ, Ye QH, Sun HJ, Jia HL, Zhu XQ, Liu DY, Chen J, Xue Q, Zhou HJ, Ren N, Qin LX. Lentiviral-mediated miRNA against osteopontin suppresses tumor growth and metastasis of human hepatocellular carcinoma. Hepatology2008; 48(6): 1834-1842
CrossRef Pubmed Google scholar
[20]
Xue YH, Zhang XF, Dong QZ, Sun J, Dai C, Zhou HJ, Ren N, Jia HL, Ye QH, Qin LX. Thrombin is a therapeutic target for metastatic osteopontin-positive hepatocellular carcinoma. Hepatology2010; 52(6): 2012-2022
CrossRef Pubmed Google scholar
[21]
Wu JC, Sun BS, Ren N, Ye QH, Qin LX. Genomic aberrations in hepatocellular carcinoma related to osteopontin expression detected by array-CGH. J Cancer Res Clin Oncol2010; 136(4): 595-601
CrossRef Pubmed Google scholar
[22]
Dong QZ, Zhang XF, Zhao Y, Jia HL, Zhou HJ, Dai C, Sun HJ, Qin Y, Zhang WD, Ren N, Ye QH, Qin LX. Osteopontin promoter polymorphisms at locus–443 significantly affect the metastasis and prognosis of human hepatocellular carcinoma. Hepatology2013; 57(3): 1024-1034
CrossRef Pubmed Google scholar
[23]
Khodavirdi AC, Song Z, Yang S, Zhong C, Wang S, Wu H, Pritchard C, Nelson PS, Roy-Burman P. Increased expression of osteopontin contributes to the progression of prostate cancer. Cancer Res2006; 66(2): 883-888
CrossRef Pubmed Google scholar
[24]
Coppola D, Szabo M, Boulware D, Muraca P, Alsarraj M, Chambers AF, Yeatman TJ. Correlation of osteopontin protein expression and pathological stage across a wide variety of tumor histologies. Clin Cancer Res2004; 10(1): 184-190
CrossRef Pubmed Google scholar
[25]
Sedivy R, Peters K, Klöppel G. Osteopontin expression in ductal adenocarcinomas and undifferentiated carcinomas of the pancreas. Virchows Arch2005; 446(1): 41-45
CrossRef Pubmed Google scholar
[26]
Mack PC, Redman MW, Chansky K, Williamson SK, Farneth NC, Lara PN Jr, Franklin WA, Le QT, Crowley JJ, Gandara DR; SWOG.Lower osteopontin plasma levels are associated with superior outcomes in advanced non-small-cell lung cancer patients receiving platinum-based chemotherapy: SWOG Study S0003. J Clin Oncol2008; 26(29): 4771-4776
CrossRef Pubmed Google scholar
[27]
Anborgh PH, Mutrie JC, Tuck AB, Chambers AF. Role of the metastasis-promoting protein osteopontin in the tumour microenvironment. J Cell Mol Med2010; 14(8): 2037-2044
CrossRef Pubmed Google scholar
[28]
Kim J, Ki SS, Lee SD, Han CJ, Kim YC, Park SH, Cho SY, Hong YJ, Park HY, Lee M, Jung HH, Lee KH, Jeong SH. Elevated plasma osteopontin levels in patients with hepatocellular carcinoma. Am J Gastroenterol2006; 101(9): 2051-2059
CrossRef Pubmed Google scholar
[29]
Pan HW, Ou YH, Peng SY, Liu SH, Lai PL, Lee PH, Sheu JC, Chen CL, Hsu HC. Overexpression of osteopontin is associated with intrahepatic metastasis, early recurrence, and poorer prognosis of surgically resected hepatocellular carcinoma. Cancer2003; 98(1): 119-127
CrossRef Pubmed Google scholar
[30]
El-Tanani MK. Role of osteopontin in cellular signaling and metastatic phenotype. Front Biosci2008; 13: 4276-4284
CrossRef Pubmed Google scholar
[31]
Ho PK, Hawkins CJ. Mammalian initiator apoptotic caspases. FEBS J2005; 272(21): 5436-5453
CrossRef Pubmed Google scholar
[32]
Gu T, Ohashi R, Cui R, Tajima K, Yoshioka M, Iwakami S, Sasaki S, Shinohara A, Matsukawa T, Kobayashi J, Inaba Y, Takahashi K. Osteopontin is involved in the development of acquired chemo-resistance of cisplatin in small cell lung cancer. Lung Cancer2009; 66(2): 176-183
CrossRef Pubmed Google scholar
[33]
Graessmann M, Berg B, Fuchs B, Klein A, Graessmann A. Chemotherapy resistance of mouse WAP-SVT/t breast cancer cells is mediated by osteopontin, inhibiting apoptosis downstream of caspase-3. Oncogene2007; 26(20): 2840-2850
CrossRef Pubmed Google scholar
[34]
Senger DR, Perruzzi CA, Gracey CF, Papadopoulos A, Tenen DG. Secreted phosphoproteins associated with neoplastic transformation: close homology with plasma proteins cleaved during blood coagulation. Cancer Res1988; 48(20): 5770-5774
Pubmed
[35]
Yokosaki Y, Matsuura N, Sasaki T, Murakami I, Schneider H, Higashiyama S, Saitoh Y, Yamakido M, Taooka Y, Sheppard D. The integrin alpha(9)beta(1) binds to a novel recognition sequence (SVVYGLR) in the thrombin-cleaved amino-terminal fragment of osteopontin. J Biol Chem1999; 274(51): 36328-36334
CrossRef Pubmed Google scholar
[36]
Helluin O, Chan C, Vilaire G, Mousa S, DeGrado WF, Bennett JS. The activation state of αvβ3 regulates platelet and lymphocyte adhesion to intact and thrombin-cleaved osteopontin. J Biol Chem2000; 275(24): 18337-18343
CrossRef Pubmed Google scholar
[37]
Senger DR, Perruzzi CA, Papadopoulos-Sergiou A, Van de Water L. Adhesive properties of osteopontin: regulation by a naturally occurring thrombin-cleavage in close proximity to the GRGDS cell-binding domain. Mol Biol Cell1994; 5(5): 565-574
CrossRef Pubmed Google scholar
[38]
Mi Z, Oliver T, Guo H, Gao C, Kuo PC. Thrombin-cleaved COOH(–) terminal osteopontin peptide binds with cyclophilin C to CD147 in murine breast cancer cells. Cancer Res2007; 67(9): 4088-4097
CrossRef Pubmed Google scholar
[39]
Nierodzik ML, Karpatkin S. Thrombin induces tumor growth, metastasis, and angiogenesis: evidence for a thrombin-regulated dormant tumor phenotype. Cancer Cell2006; 10(5): 355-362
CrossRef Pubmed Google scholar
[40]
Hu L, Lee M, Campbell W, Perez-Soler R, Karpatkin S. Role of endogenous thrombin in tumor implantation, seeding, and spontaneous metastasis. Blood2004; 104(9): 2746-2751
CrossRef Pubmed Google scholar
[41]
Singhal H, Bautista DS, Tonkin KS, O’Malley FP, Tuck AB, Chambers AF, Harris JF. Elevated plasma osteopontin in metastatic breast cancer associated with increased tumor burden and decreased survival. Clin Cancer Res1997; 3(4): 605-611
Pubmed
[42]
Blasberg JD, Pass HI, Goparaju CM, Flores RM, Lee S, Donington JS. Reduction of elevated plasma osteopontin levels with resection of non-small-cell lung cancer. J Clin Oncol2010; 28(6): 936-941
CrossRef Pubmed Google scholar
[43]
Zhao J, Dong L, Lu B, Wu G, Xu D, Chen J, Li K, Tong X, Dai J, Yao S, Wu M, Guo Y. Down-regulation of osteopontin suppresses growth and metastasis of hepatocellular carcinoma via induction of apoptosis. Gastroenterology2008; 135(3): 956-968
CrossRef Pubmed Google scholar
[44]
Smith LL, Cheung HK, Ling LE, Chen J, Sheppard D, Pytela R, Giachelli CM. Osteopontin N-terminal domain contains a cryptic adhesive sequence recognized by α9β1 integrin. J Biol Chem1996; 271(45): 28485-28491
CrossRef Pubmed Google scholar
[45]
Senger DR, Perruzzi CA. Cell migration promoted by a potent GRGDS-containing thrombin-cleavage fragment of osteopontin. Biochim Biophys Acta1996; 1314(1-2): 13-24
CrossRef Pubmed Google scholar
[46]
Hasegawa M, Nakoshi Y, Iino T, Sudo A, Segawa T, Maeda M, Yoshida T, Uchida A. Thrombin-cleaved osteopontin in synovial fluid of subjects with rheumatoid arthritis. J Rheumatol2009; 36(2): 240-245
CrossRef Pubmed Google scholar
[47]
Radjabi AR, Sawada K, Jagadeeswaran S, Eichbichler A, Kenny HA, Montag A, Bruno K, Lengyel E. Thrombin induces tumor invasion through the induction and association of matrix metalloproteinase-9 andβ1-integrin on the cell surface. J Biol Chem2008; 283(5): 2822-2834
CrossRef Pubmed Google scholar
[48]
Young MF, Kerr JM, Termine JD, Wewer UM, Wang MG, McBride OW, Fisher LW. cDNA cloning, mRNA distribution and heterogeneity, chromosomal location, and RFLP analysis of human osteopontin (OPN). Genomics1990; 7(4): 491-502
CrossRef Pubmed Google scholar
[49]
Naito M, Matsui A, Inao M, Nagoshi S, Nagano M, Ito N, Egashira T, Hashimoto M, Mishiro S, Mochida S, Fujiwara K. SNPs in the promoter region of the osteopontin gene as a marker predicting the efficacy of interferon-based therapies in patients with chronic hepatitis C. J Gastroenterol2005; 40(4): 381-388
CrossRef Pubmed Google scholar
[50]
Giacopelli F, Marciano R, Pistorio A, Catarsi P, Canini S, Karsenty G, Ravazzolo R. Polymorphisms in the osteopontin promoter affect its transcriptional activity. Physiol Genomics2004; 20(1): 87-96
CrossRef Pubmed Google scholar
[51]
Hendig D, Arndt M, Szliska C, Kleesiek K, Götting C. SPP1 promoter polymorphisms: identification of the first modifier gene for pseudoxanthoma elasticum. Clin Chem2007; 53(5): 829-836
CrossRef Pubmed Google scholar
[52]
Liu CC, Huang SP, Tsai LY, Wu WJ, Juo SH, Chou YH, Huang CH, Wu MT. The impact of osteopontin promoter polymorphisms on the risk of calcium urolithiasis. Clin Chim Acta2010; 411(9-10): 739-743
CrossRef Pubmed Google scholar
[53]
D’Alfonso S, Barizzone N, Giordano M, Chiocchetti A, Magnani C, Castelli L, Indelicato M, Giacopelli F, Marchini M, Scorza R, Danieli MG, Cappelli M, Migliaresi S, Bigliardo B, Sabbadini MG, Baldissera E, Galeazzi M, Sebastiani GD, Minisola G, Ravazzolo R, Dianzani U, Momigliano-Richiardi P. Two single-nucleotide polymorphisms in the 5′ and 3′ ends of the osteopontin gene contribute to susceptibility to systemic lupus erythematosus. Arthritis Rheum2005; 52(2): 539-547
CrossRef Pubmed Google scholar
[54]
Chiu YW, Tu HF, Wang IK, Wu CH, Chang KW, Liu TY, Kao SY. The implication of osteopontin (OPN) expression and genetic polymorphisms of OPN promoter in oral carcinogenesis. Oral Oncol2010; 46(4): 302-306
CrossRef Pubmed Google scholar
[55]
El-Tanani MK, Campbell FC, Kurisetty V, Jin D, McCann M, Rudland PS. The regulation and role of osteopontin in malignant transformation and cancer. Cytokine Growth Factor Rev2006; 17(6): 463-474
CrossRef Pubmed Google scholar
[56]
Mochida S, Hashimoto M, Matsui A, Naito M, Inao M, Nagoshi S, Nagano M, Egashira T, Mishiro S, Fujiwara K. Genetic polymorphims in promoter region of osteopontin gene may be a marker reflecting hepatitis activity in chronic hepatitis C patients. Biochem Biophys Res Commun2004; 313(4): 1079-1085
CrossRef Pubmed Google scholar
[57]
Sakaki M, Makino R, Hiroishi K, Ueda K, Eguchi J, Hiraide A, Doi H, Omori R, Imawari M. Cyclooxygenase-2 gene promoter polymorphisms affect susceptibility to hepatitis C virus infection and disease progression. Hepatol Res2010; 40(12): 1219-1226
CrossRef Pubmed Google scholar
[58]
Shaker OG, Sadik NA, El-Dessouki A. Single-nucleotide polymorphism in the promoter region of the osteopontin gene at nucleotide –443 as a marker predicting the efficacy of pegylated interferon/ribavirin-therapy in Egyptians patients with chronic hepatitis C. Hum Immunol2012; 73(10): 1039-1045
CrossRef Pubmed Google scholar
[59]
Yamamoto S, Hijiya N, Setoguchi M, Matsuura K, Ishida T, Higuchi Y, Akizuki S. Structure of the osteopontin gene and its promoter. Ann N Y Acad Sci1995; 760(1 Osteopontin): 44-58
CrossRef Pubmed Google scholar
[60]
Schultz J, Lorenz P, Ibrahim SM, Kundt G, Gross G, Kunz M. The functional –443T/C osteopontin promoter polymorphism influences osteopontin gene expression in melanoma cells via binding of c-Myb transcription factor. Mol Carcinog2009; 48(1): 14-23
CrossRef Pubmed Google scholar
[61]
Shang S, Plymoth A, Ge S, Feng Z, Rosen HR, Sangrajrang S, Hainaut P, Marrero JA, Beretta L. Identification of osteopontin as a novel marker for early hepatocellular carcinoma. Hepatology2012; 55(2): 483-490
CrossRef Pubmed Google scholar

RIGHTS & PERMISSIONS

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg
AI Summary AI Mindmap
PDF(298 KB)

Accesses

Citations

Detail

Sections
Recommended

/