Protein tyrosine phosphatase receptor type O expression in the tumor niche correlates with reduced tumor growth, angiogenesis, circulating tumor cells and metastasis of breast cancer

Liu,Zhao; Hou,Jiajie; Ren,Lidong; He,Jing; Sun,Beicheng; Sun,Lu-Zhe; Wang,Shui

doi:10.3892/or.2015.3772

April-2015 Volume 33 Issue 4

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April-2015 Volume 33 Issue 4

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Article

Protein tyrosine phosphatase receptor type O expression in the tumor niche correlates with reduced tumor growth, angiogenesis, circulating tumor cells and metastasis of breast cancer

Authors:
- Zhao Liu
- Jiajie Hou
- Lidong Ren
- Jing He
- Beicheng Sun
- Lu-Zhe Sun
- Shui Wang
View Affiliations / Copyright

Affiliations: Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA
Pages: 1908-1914
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Published online on: January 29, 2015

https://doi.org/10.3892/or.2015.3772
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Abstract

Protein tyrosine phosphatase receptor type O (PTPRO) has been recognized as a tumor suppressor in various types of cancer cells. However, little attention has been given to the role of PTPRO expression in the tumor microenvironment. We aimed to reveal the role of PTPRO in the breast cancer niche. Py8119 mouse breast cancer cells were implanted orthotopically into female wild-type or ptpro-/- C57Bl/6 mice. We observed that the loss of PTPRO in the tumor niche was correlated with larger tumor volume, more metastases, increased number of circulating tumor cells (CTCs), less apoptosis and reduced necrosis rates in the orthotopic mouse model of breast cancer. The tumor microenvironment in the ptpro-/- mice also showed increased microvessel density. Moreover, an intracardiac injection mouse model was used to determine the role of PTPRO in the pre-metastatic niche. Notably, more metastases were observed in the mice of the ptpro-/- group. Taken together, PTPRO expression in the tumor niche prevents tumor growth and the formation of metastases of breast cancer, in part by attenuating tumor-associated angiogenesis and inducing the apoptosis and necrosis of tumor cells.

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1	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI
2	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
3	Paget S: The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev. 8:98–101. 1989.PubMed/NCBI
4	Thomas PE, Wharram BL, Goyal M, Wiggins JE, Holzman LB and Wiggins RC: GLEPP1, a renal glomerular epithelial cell (podocyte) membrane protein-tyrosine phosphatase. Identification, molecular cloning, and characterization in rabbit. J Biol Chem. 269:19953–19962. 1994.PubMed/NCBI
5	Jiang R, Xia Y, Li J, et al: High expression levels of IKKalpha and IKKbeta are necessary for the malignant properties of liver cancer. Int J Cancer. 126:1263–1274. 2010.
6	Seimiya H and Tsuruo T: Functional involvement of PTP-U2L in apoptosis subsequent to terminal differentiation of monoblastoid leukemia cells. J Biol Chem. 273:21187–21193. 1998. View Article : Google Scholar : PubMed/NCBI
7	Motiwala T, Kutay H, Ghoshal K, et al: Protein tyrosine phosphatase receptor-type O (PTPRO) exhibits characteristics of a candidate tumor suppressor in human lung cancer. Proc Natl Acad Sci USA. 101:13844–13849. 2004. View Article : Google Scholar : PubMed/NCBI
8	Motiwala T, Majumder S, Kutay H, et al: Methylation and silencing of protein tyrosine phosphatase receptor type O in chronic lymphocytic leukemia. Clin Cancer Res. 13:3174–3181. 2007. View Article : Google Scholar : PubMed/NCBI
9	Gibby K, You WK, Kadoya K, et al: Early vascular deficits are correlated with delayed mammary tumorigenesis in the MMTV-PyMT transgenic mouse following genetic ablation of the NG2 proteoglycan. Breast Cancer Res. 14:R672012. View Article : Google Scholar : PubMed/NCBI
10	Hou J, Xu J, Jiang R, et al: Estrogen-sensitive PTPRO expression represses hepatocellular carcinoma progression by control of STAT3. Hepatology. 57:678–688. 2013. View Article : Google Scholar
11	Liu Z, Bandyopadhyay A, Nichols RW, et al: Blockade of autocrine TGF-β signaling inhibits stem cell phenotype, survival, and metastasis of murine breast cancer cells. J Stem Cell Res Ther. 2:1–8. 2012. View Article : Google Scholar
12	Carvalho MI, Guimaraes MJ, Pires I, et al: EGFR and microvessel density in canine malignant mammary tumours. Res Vet Sci. 95:1094–1099. 2013. View Article : Google Scholar : PubMed/NCBI
13	Mao Y, Keller ET, Garfield DH, Shen K and Wang J: Stromal cells in tumor microenvironment and breast cancer. Cancer Metastasis Rev. 32:303–315. 2013. View Article : Google Scholar
14	Motiwala T, Ghoshal K, Das A, et al: Suppression of the protein tyrosine phosphatase receptor type O gene (PTPRO) by methylation in hepatocellular carcinomas. Oncogene. 22:6319–6331. 2003. View Article : Google Scholar : PubMed/NCBI
15	Huang YT, Li FF, Ke C, et al: PTPRO promoter methylation is predictive of poorer outcome for HER2-positive breast cancer: indication for personalized therapy. J Transl Med. 11:2452013. View Article : Google Scholar : PubMed/NCBI
16	Li SY, Li R, Chen YL, et al: Aberrant PTPRO methylation in tumor tissues as a potential biomarker that predicts clinical outcomes in breast cancer patients. BMC Genet. 15:672014. View Article : Google Scholar : PubMed/NCBI
17	Derycke L, Van MV, Depypere H and Bracke M: Molecular targets of growth, differentiation, tissue integrity, and ectopic cell death in cancer cells. Cancer Biother Radiopharm. 20:579–588. 2005. View Article : Google Scholar
18	Kopfstein L and Christofori G: Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment. Cell Mol Life Sci. 63:449–468. 2006. View Article : Google Scholar : PubMed/NCBI
19	Lorusso G and Ruegg C: New insights into the mechanisms of organ-specific breast cancer metastasis. Semin Cancer Biol. 22:226–233. 2012. View Article : Google Scholar : PubMed/NCBI
20	Cai J, Chen Z, Ruan Q, et al: γ-secretase and presenilin mediate cleavage and phosphorylation of vascular endothelial growth factor receptor-1. J Biol Chem. 286:42514–42523. 2011. View Article : Google Scholar : PubMed/NCBI
21	Chen JX, Tuo Q, Liao DF and Zeng H: Inhibition of protein tyrosine phosphatase improves angiogenesis via enhancing Ang-1/Tie-2 signaling in diabetes. Exp Diabetes Res. 2012:8367592012. View Article : Google Scholar : PubMed/NCBI
22	Alemar J and Schuur ER: Progress in using circulating tumor cell information to improve metastatic breast cancer therapy. J Oncol. 2013:7027322013. View Article : Google Scholar : PubMed/NCBI
23	Paterlini-Brechot P and Benali NL: Circulating tumor cell (CTC) detection: clinical impact and future directions. Cancer Lett. 253:180–204. 2007. View Article : Google Scholar : PubMed/NCBI
24	Chang YS, di Tomaso E, McDonald DM, Jones R, Jain RK and Munn LL: Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood. Proc Natl Acad Sci USA. 97:14608–14613. 2000. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Protein tyrosine phosphatase receptor type O expression in the tumor niche correlates with reduced tumor growth, angiogenesis, circulating tumor cells and metastasis of breast cancer

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Abstract

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