Review
. 2006 Nov; 17(6):463-74.
doi: 10.1016/j.cytogfr.2006.09.010.

The regulation and role of osteopontin in malignant transformation and cancer

Mohamed K El-Tanani 1 Frederick Charles Campbell  Vittal Kurisetty  Dachuan Jin  Mella McCann  Philip S Rudland  
Affiliations
  • PMID: 17113338
  •     66 citations

Abstract

Osteopontin (OPN) is a predominantly secreted extracellular matrix glycophosphoprotein which binds to alpha v-containing integrins and has an important role in malignant cell attachment and invasion. High OPN expression in the primary tumor is associated with early metastasis and poor outcome in human breast and other cancers. Forced OPN overexpression in benign cells may induce neoplastic-like cell behaviour including increased attachment and invasion in vitro as well as the ability to metastasize in vivo. Conversely, OPN inhibition by antisense cDNA impedes cell growth and tumor forming capacity. OPN is not mutationally activated in cancer but its expression is regulated by Wnt/Tcf signaling, steroid receptors, growth factors, ras, Ets and AP-1 transcription factors. Presumably these factors are implicated in induction of OPN overexpression in cancer. Greater understanding of the role of OPN in neoplastic change and its transcriptional regulation may enable development of novel cancer treatment strategies.

Molecular mechanisms linking wound inflammation and fibrosis: knockdown of osteopontin leads to rapid repair and reduced scarring.
Ryoichi Mori, Tanya J Shaw, Paul Martin.
J Exp Med, 2008 Jan 09; 205(1). PMID: 18180311    Free PMC article.
Highly Cited.
Pathway analysis of primary central nervous system lymphoma.
Han W Tun, David Personett, +9 authors, Michael McKinney.
Blood, 2008 Jan 11; 111(6). PMID: 18184868    Free PMC article.
Development of fragment-specific osteopontin antibodies and ELISA for quantification in human metastatic breast cancer.
Alicia Plumer, Hongyi Duan, +4 authors, Lucy Liaw.
BMC Cancer, 2008 Feb 02; 8. PMID: 18237408    Free PMC article.
Small integrin-binding ligand N-linked glycoproteins (SIBLINGs): multifunctional proteins in cancer.
Akeila Bellahcène, Vincent Castronovo, +2 authors, Neal S Fedarko.
Nat Rev Cancer, 2008 Feb 23; 8(3). PMID: 18292776    Free PMC article.
Highly Cited. Review.
Identification of osteopontin as the most consistently over-expressed gene in intrahepatic cholangiocarcinoma: detection by oligonucleotide microarray and real-time PCR analysis.
Holger G Hass, Oliver Nehls, +3 authors, Stephan Kaiser.
World J Gastroenterol, 2008 Apr 30; 14(16). PMID: 18442196    Free PMC article.
Osteopontin is not critical for otoconia formation or balance function.
Xing Zhao, Sherri M Jones, Wallace B Thoreson, Yunxia Wang Lundberg.
J Assoc Res Otolaryngol, 2008 May 07; 9(2). PMID: 18459000    Free PMC article.
Microarray analysis identifies a common set of cellular genes modulated by different HCV replicon clones.
Anna Rita Ciccaglione, Cinzia Marcantonio, +7 authors, Maria Rapicetta.
BMC Genomics, 2008 Jul 02; 9. PMID: 18590516    Free PMC article.
Potential relationship between hepatobiliary osteopontin and peroxisome proliferator-activated receptor alpha expression following ethanol-associated hepatic injury in vivo and in vitro.
Jin-Hyung Lee, Atrayee Banerjee, Yoshi Ueno, Shashi K Ramaiah.
Toxicol Sci, 2008 Aug 16; 106(1). PMID: 18703563    Free PMC article.
Structural requirements for bone sialoprotein binding and modulation of matrix metalloproteinase-2.
Alka Jain, Abdullah Karadag, Larry W Fisher, Neal S Fedarko.
Biochemistry, 2008 Aug 30; 47(38). PMID: 18729384    Free PMC article.
A role of fukutin, a gene responsible for Fukuyama type congenital muscular dystrophy, in cancer cells: a possible role to suppress cell proliferation.
Tomoko Yamamoto, Yoichiro Kato, +3 authors, Makio Kobayashi.
Int J Exp Pathol, 2008 Sep 24; 89(5). PMID: 18808525    Free PMC article.
Insights into the biology of primary central nervous system lymphoma.
Maciej M Mrugala, James L Rubenstein, Maurilio Ponzoni, Tracy T Batchelor.
Curr Oncol Rep, 2008 Dec 17; 11(1). PMID: 19080745    Free PMC article.
Review.
Cancer and the tumor microenvironment: a review of an essential relationship.
Flaubert Mbeunkui, Donald J Johann.
Cancer Chemother Pharmacol, 2008 Dec 17; 63(4). PMID: 19083000    Free PMC article.
Highly Cited. Review.
Identification of a biphasic role for genistein in the regulation of prostate cancer growth and metastasis.
Lara H El Touny, Partha P Banerjee.
Cancer Res, 2009 Apr 09; 69(8). PMID: 19351854    Free PMC article.
Osteopontin: a multifunctional protein at the crossroads of inflammation, atherosclerosis, and vascular calcification.
Hyun-Ju Cho, Hyun-Jai Cho, Hyo-Soo Kim.
Curr Atheroscler Rep, 2009 Apr 14; 11(3). PMID: 19361352
Review.
Identification of osteopontin-dependent signaling pathways in a mouse model of human breast cancer.
Zhiyong Mi, Hongtao Guo, Paul C Kuo.
BMC Res Notes, 2009 Jul 03; 2. PMID: 19570203    Free PMC article.
Immunohistochemical expression of osteopontin in gastric cancer.
Motohiro Imano, Takao Satou, +12 authors, Harumasa Ohyanagi.
J Gastrointest Surg, 2009 Jul 08; 13(9). PMID: 19582521
Lessons in signaling and tumorigenesis from polyomavirus middle T antigen.
Michele M Fluck, Brian S Schaffhausen.
Microbiol Mol Biol Rev, 2009 Sep 02; 73(3). PMID: 19721090    Free PMC article.
Review.
The role of osteopontin in inflammatory processes.
Susan Amanda Lund, Cecilia M Giachelli, Marta Scatena.
J Cell Commun Signal, 2009 Oct 03; 3(3-4). PMID: 19798593    Free PMC article.
Highly Cited.
PD-1+ memory phenotype CD4+ T cells expressing C/EBPalpha underlie T cell immunodepression in senescence and leukemia.
Kenichiro Shimatani, Yasuhiro Nakashima, +2 authors, Nagahiro Minato.
Proc Natl Acad Sci U S A, 2009 Oct 07; 106(37). PMID: 19805226    Free PMC article.
Osteopontin induces beta-catenin signaling through activation of Akt in prostate cancer cells.
Brian W Robertson, Meenakshi A Chellaiah.
Exp Cell Res, 2009 Oct 24; 316(1). PMID: 19850036    Free PMC article.
Gene expression profiling of paraffin-embedded primary melanoma using the DASL assay identifies increased osteopontin expression as predictive of reduced relapse-free survival.
Caroline Conway, Angana Mitra, +13 authors, Julia Newton-Bishop.
Clin Cancer Res, 2009 Nov 06; 15(22). PMID: 19887478    Free PMC article.
Elevated phosphate activates N-ras and promotes cell transformation and skin tumorigenesis.
Corinne E Camalier, Matthew R Young, +3 authors, George R Beck.
Cancer Prev Res (Phila), 2010 Feb 11; 3(3). PMID: 20145188    Free PMC article.
Elevated osteopontin expression and proliferative/apoptotic ratio in the colorectal adenoma-dysplasia-carcinoma sequence.
Gábor Valcz, Ferenc Sipos, +8 authors, Zsolt Tulassay.
Pathol Oncol Res, 2010 Mar 30; 16(4). PMID: 20349162
Melanoma sentinel node biopsy and prediction models for relapse and overall survival.
A Mitra, C Conway, +17 authors, J A Newton-Bishop.
Br J Cancer, 2010 Sep 23; 103(8). PMID: 20859289    Free PMC article.
Expression of osteopontin coregulators in primary colorectal cancer and associated liver metastases.
D J Mole, C O'Neill, +6 authors, F C Campbell.
Br J Cancer, 2011 Feb 24; 104(6). PMID: 21343932    Free PMC article.
Elevated content of osteopontin in plasma and tumor tissues of patients with laryngeal and hypopharyngeal carcinoma associated with metastasis and prognosis.
Yong Li, Liang Li, +2 authors, Jian Guang Lu.
Med Oncol, 2011 Jun 28; 29(3). PMID: 21706367
Osteopontin, an oxidant stress sensitive cytokine, up-regulates collagen-I via integrin α(V)β(3) engagement and PI3K/pAkt/NFκB signaling.
Raquel Urtasun, Aritz Lopategi, +6 authors, Natalia Nieto.
Hepatology, 2011 Sep 29; 55(2). PMID: 21953216    Free PMC article.
DNAJB6 chaperones PP2A mediated dephosphorylation of GSK3β to downregulate β-catenin transcription target, osteopontin.
A Mitra, M E Menezes, +4 authors, R S Samant.
Oncogene, 2012 Jan 24; 31(41). PMID: 22266849    Free PMC article.
Wnt pathway inhibition via the targeting of Frizzled receptors results in decreased growth and tumorigenicity of human tumors.
Austin Gurney, Fumiko Axelrod, +20 authors, Timothy Hoey.
Proc Natl Acad Sci U S A, 2012 Jul 04; 109(29). PMID: 22753465    Free PMC article.
Highly Cited.
EGFR expression is linked to osteopontin and Nf-κB signaling in clear cell renal cell carcinoma.
K Matušan-Ilijaš, G Damante, +7 authors, K Lučin.
Clin Transl Oncol, 2012 Aug 03; 15(1). PMID: 22855173
Significance of plasma osteopontin levels in patients with bladder urothelial carcinomas.
Li Zhao, Yalin Wang, +2 authors, Lijun Chen.
Mol Diagn Ther, 2012 Oct 12; 16(5). PMID: 23055388
Genetic polymorphisms in the osteopontin promoter increases the risk of distance metastasis and death in Chinese patients with gastric cancer.
Fujun Zhao, Xiaoyi Chen, +3 authors, Guoxin Zhang.
BMC Cancer, 2012 Oct 18; 12. PMID: 23072570    Free PMC article.
Thrombin-cleaved fragments of osteopontin are overexpressed in malignant glial tumors and provide a molecular niche with survival advantage.
Yasuto Yamaguchi, Zhifei Shao, +8 authors, Lawrence L K Leung.
J Biol Chem, 2012 Dec 04; 288(5). PMID: 23204518    Free PMC article.
Apoptosis and angiogenesis: an evolving mechanism for fibrosis.
Ariel Johnson, Luisa Ann DiPietro.
FASEB J, 2013 Jun 21; 27(10). PMID: 23783074    Free PMC article.
Review.
Association between polymorphisms in osteopontin gene (SPP1) and first episode calcium oxalate urolithiasis.
Mohammad Reza Safarinejad, Nayyer Shafiei, Shiva Safarinejad.
Urolithiasis, 2013 Jun 21; 41(4). PMID: 23784265
Osteopontin is a promoter for hepatocellular carcinoma metastasis: a summary of 10 years of studies.
Lunxiu Qin.
Front Med, 2014 Jan 28; 8(1). PMID: 24464486
Review.
Inorganic phosphate induces cancer cell mediated angiogenesis dependent on forkhead box protein C2 (FOXC2) regulated osteopontin expression.
Yiming Lin, Kelly E McKinnon, Shin Woo Ha, George R Beck.
Mol Carcinog, 2014 Apr 05; 54(9). PMID: 24700685    Free PMC article.
Circulating glioma biomarkers.
Johan M Kros, Dana M Mustafa, +3 authors, Ping-Pin Zheng.
Neuro Oncol, 2014 Sep 26; 17(3). PMID: 25253418    Free PMC article.
Review.
Osteopontin (OPN) isoforms, diabetes, obesity, and cancer; what is one got to do with the other? A new role for OPN.
Konrad Sarosiek, Elizabeth Jones, +7 authors, Hwyda A Arafat.
J Gastrointest Surg, 2015 Jan 15; 19(4). PMID: 25583441
Functional characterization of OPN in human laryngeal squamous cell carcinoma and its xenograft model in nude mice.
Jianqiu Chen, Qi Zhou, +5 authors, Hongliang Zheng.
Int J Clin Exp Med, 2015 Mar 19; 8(1). PMID: 25784985    Free PMC article.
Evaluation of copy number variation and gene expression in neurofibromatosis type-1-associated malignant peripheral nerve sheath tumours.
Laura E Thomas, Jincy Winston, +7 authors, Meena Upadhyaya.
Hum Genomics, 2015 Apr 18; 9. PMID: 25884485    Free PMC article.
Neutralization of osteopontin attenuates neutrophil migration in sepsis-induced acute lung injury.
Yohei Hirano, Monowar Aziz, +5 authors, Ping Wang.
Crit Care, 2015 Apr 19; 19. PMID: 25887405    Free PMC article.
The role of osteopontin expression in melanoma progression.
Timea Kiss, Szilvia Ecsedi, +5 authors, Margit Balazs.
Tumour Biol, 2015 May 07; 36(10). PMID: 25944164
Post-operative plasma osteopontin predicts distant metastasis in human colorectal cancer.
Lui Ng, Timothy Ming-Hun Wan, +14 authors, Wai-Lun Law.
PLoS One, 2015 May 12; 10(5). PMID: 25961724    Free PMC article.
SNPs in the promoter region of the osteopontin gene as a possible host factor for sex difference in hepatocellular carcinoma development in patients with HCV.
Kazuhiro Hamaoka, Sumiko Nagoshi, +6 authors, Satoshi Mochida.
Hepatol Int, 2013 Jun 01; 7(2). PMID: 26201802
Association of OPN overexpression with tumor stage, differentiation, metastasis and tumor progression in human laryngeal squamous cell carcinoma.
Jianqiu Chen, Chunsheng Zhu, +4 authors, Fenghua Zhang.
Int J Clin Exp Med, 2015 Jul 30; 8(5). PMID: 26221249    Free PMC article.
Association between promoter polymorphisms of OPN gene and cancer risk: a meta-analysis.
Jingwei Liu, Caiyun He, +3 authors, Yuan Yuan.
Onco Targets Ther, 2016 Jan 15; 9. PMID: 26766914    Free PMC article.
Neutralization of Osteopontin Ameliorates Acute Lung Injury Induced by Intestinal Ischemia-Reperfusion.
Yohei Hirano, Monowar Aziz, +2 authors, Ping Wang.
Shock, 2016 Mar 15; 46(4). PMID: 26974422    Free PMC article.
Expression of the SIBLINGs and their MMP partners in human benign and malignant prostate neoplasms.
Charles C Anunobi, Komal Koli, +2 authors, Kalu U E Ogbureke.
Oncotarget, 2016 Jun 23; 7(30). PMID: 27331624    Free PMC article.
Cancer Secretome May Influence BSP and DSP Expression in Human Salivary Gland Cells.
Samantha Lynn Hamilton, Blake Ferando, +2 authors, Anita Rose Joy.
J Histochem Cytochem, 2016 Nov 25; 65(3). PMID: 27881474    Free PMC article.
NF‑κB inhibition is associated with OPN/MMP‑9 downregulation in cutaneous melanoma.
Claudio Guarneri, Valentina Bevelacqua, +5 authors, Massimo Libra.
Oncol Rep, 2017 Jan 12; 37(2). PMID: 28075446    Free PMC article.
Osteopontin improves adhesion and migration of human primary renal cortical epithelial cells during wound healing.
Jinfeng Wu, Zuolin Wang.
Oncol Lett, 2017 Jan 20; 12(6). PMID: 28101213    Free PMC article.
Monocyte Chemotactic Protein-1-Interleukin-6-Osteopontin Pathway of Intra-Aneurysmal Tissue Healing.
Koji Hosaka, Kelley Rojas, +6 authors, Brian Hoh.
Stroke, 2017 Mar 16; 48(4). PMID: 28292871    Free PMC article.
Induction of Osteopontin by Dengue Virus-3 Infection in THP-1 Cells: Inhibition of the Synthesis by Brefelamide and Its Derivative.
Dyshelly N Pascapurnama, Hannah K M Labayo, +9 authors, Toshio Hattori.
Front Microbiol, 2017 Apr 14; 8. PMID: 28405192    Free PMC article.
Human osteopontin: Potential clinical applications in cancer (Review).
Chengcheng Hao, Yuxin Cui, +3 authors, Wen G Jiang.
Int J Mol Med, 2017 Apr 26; 39(6). PMID: 28440483    Free PMC article.
Review.
Osteopontin is Critical for Hyperactive mTOR-Induced Tumorigenesis in Oral Squamous Cell Carcinoma.
Ning Gan, Sihai Zou, +3 authors, Yibing Yin.
J Cancer, 2017 Jun 24; 8(8). PMID: 28638450    Free PMC article.
Osteopontin -- a promising biomarker for cancer therapy.
Ran Wei, Janet Pik Ching Wong, Hang Fai Kwok.
J Cancer, 2017 Aug 19; 8(12). PMID: 28819419    Free PMC article.
Review.
Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers.
Joshua D Cohen, Ammar A Javed, +37 authors, Anne Marie Lennon.
Proc Natl Acad Sci U S A, 2017 Sep 07; 114(38). PMID: 28874546    Free PMC article.
Highly Cited.
Osteopontin activates mesenchymal stem cells to repair skin wound.
Wenping Wang, Pei Li, +4 authors, Zhenxiang Wang.
PLoS One, 2017 Sep 29; 12(9). PMID: 28957406    Free PMC article.
The prognostic value of osteopontin in limited-stage small cell lung cancer patients and its mechanism.
Fanglei Liu, Chunxue Bai, Zhongliang Guo.
Oncotarget, 2017 Oct 21; 8(41). PMID: 29050263    Free PMC article.
Isoform-specific promotion of breast cancer tumorigenicity by TBX3 involves induction of angiogenesis.
Milica Krstic, Haider M Hassan, +6 authors, Alan B Tuck.
Lab Invest, 2019 Oct 02; 100(3). PMID: 31570773    Free PMC article.
Gene Expression Changes Accompanying the Duodenal Adenoma-Carcinoma Sequence in Familial Adenomatous Polyposis.
Sushrut S Thiruvengadam, Margaret OʼMalley, +12 authors, Carol A Burke.
Clin Transl Gastroenterol, 2019 Jun 19; 10(6). PMID: 31211760    Free PMC article.
Stimulation of THP-1 Macrophages with LPS Increased the Production of Osteopontin-Encapsulating Exosome.
Gaowa Bai, Takashi Matsuba, Toshiro Niki, Toshio Hattori.
Int J Mol Sci, 2020 Nov 15; 21(22). PMID: 33187327    Free PMC article.
Evaluation of local and circulating osteopontin in malignant and benign primary bone tumors.
Ali Nazarizadeh, Shahin Alizadeh-Fanalou, +7 authors, Masoumeh Tavakoli-Yaraki.
J Bone Oncol, 2021 Jul 09; 29. PMID: 34235049    Free PMC article.
Osteogenic Differentiation of Mesenchymal Stem Cells via Curcumin-Containing Nanoscaffolds.
Khadijeh Khezri, Solmaz Maleki Dizaj, +6 authors, Farzaneh Lotfipour.
Stem Cells Int, 2021 Aug 03; 2021. PMID: 34335789    Free PMC article.
Review.
Diminished PLK2 Induces Cardiac Fibrosis and Promotes Atrial Fibrillation.
Stephan R Künzel, Maximilian Hoffmann, +29 authors, Ali El-Armouche.
Circ Res, 2021 Aug 27; 129(8). PMID: 34433292    Free PMC article.