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World Journal of Surgical Oncology

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Open Access 01-12-2016 | Research

SDF-1/CXCR7 axis regulates the proliferation, invasion, adhesion, and angiogenesis of gastric cancer cells

Authors: De-Min Ma, Dian-Xi Luo, Jie Zhang

Published in: World Journal of Surgical Oncology | Issue 1/2016

Abstract

Background

More recent studies have revealed that chemokine receptor CXCR7 plays an important role in cancer development. However, little is known about the effect of CXCR7 on the process of gastric cancer cell invasion and angiogenesis. The aim of this study is to investigate the expression of CXCR7 in gastric cancer cell lines and to evaluate the role of CXCR7 in the proliferation, invasion, adhesion, and angiogenesis of gastric cancer cells.

Methods

Real-time PCR and Western blotting were used to examine the mRNA and protein levels of CXCR4 and CXCR7 in five gastric cancer cell lines (HGC-27, MGC-803, BGC-823, SGC-7901, and MKN-28). CXCR7-expressing shRNA was constructed and subsequently stably transfected into the human gastric cancer cells. In addition, the effect of CXCR7 inhibition on cell proliferation, invasion, adhesion, VEGF secretion, and tube formation was evaluated.

Results

The mRNA and protein of CXCR7 were expressed in all five gastric cancer cell lines; in particular, the expression of CXCR7 was the highest in SGC-7901 cells. Stromal cell-derived factor-1 (SDF-1) was found to induce proliferation, invasion, adhesion, and tube formation. Moreover, the VEGF secretion in SGC-7901 cells was also enhanced by SDF-1 stimulation. These biological effects were inhibited by the silencing of CXCR7 in SGC-7901 cells.

Conclusions

Increased CXCR7 expression was found in gastric cancer cells. Knockdown of CXCR7 expression by transfection with CXCR7shRNA significantly inhibits SGC-7901 cells’ proliferation, invasion, adhesion, and angiogenesis. This study provides new insights into the significance of CXCR7 in the invasion and angiogenesis of gastric cancer.

Shen L, Shan YS, Hu HM, Price TJ, Sirohi B, Yeh KH, Yang YH, Sano T, Yang HK, Zhang X, et al. Management of gastric cancer in Asia: resource-stratified guidelines. Lancet Oncol. 2013;14:e535–47.CrossRefPubMed

Mihmanli M, Ilhan E, Idiz UO, Alemdar A, Demir U. Recent developments and innovations in gastric cancer. World J Gastroenterol. 2016;22:4307–20.CrossRefPubMedPubMedCentral

Doring Y, Pawig L, Weber C, Noels H. The CXCL12/CXCR4 chemokine ligand/receptor axis in cardiovascular disease. Front Physiol. 2014;5:212.PubMedPubMedCentral

Schonemeier B, Kolodziej A, Schulz S, Jacobs S, Hoellt V, Stumm R. Regional and cellular localization of the CXCl12/SDF-1 chemokine receptor CXCR7 in the developing and adult rat brain. J Comp Neurol. 2008;510:207–20.CrossRefPubMed

Peled A, Grabovsky V, Habler L, Sandbank J, Arenzana-Seisdedos F, Petit I, Ben-Hur H, Lapidot T, Alon R. The chemokine SDF-1 stimulates integrin-mediated arrest of CD34(+) cells on vascular endothelium under shear flow. J Clin Invest. 1999;104:1199–211.CrossRefPubMedPubMedCentral

Pawig L, Klasen C, Weber C, Bernhagen J, Noels H. Diversity and inter-connections in the CXCR4 chemokine receptor/ligand family: molecular perspectives. Front Immunol. 2015;6:429.CrossRefPubMedPubMedCentral

Chen T, Bai H, Shao Y, Arzigian M, Janzen V, Attar E, Xie Y, Scadden DT, Wang ZZ. Stromal cell-derived factor-1/CXCR4 signaling modifies the capillary-like organization of human embryonic stem cell-derived endothelium in vitro. Stem Cells. 2007;25:392–401.CrossRefPubMed

Nagasawa T, Hirota S, Tachibana K, Takakura N, Nishikawa S, Kitamura Y, Yoshida N, Kikutani H, Kishimoto T. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature. 1996;382:635–8.CrossRefPubMed

Balkwill F. The significance of cancer cell expression of the chemokine receptor CXCR4. Semin Cancer Biol. 2004;14:171–9.CrossRefPubMed

10.

Dewan MZ, Ahmed S, Iwasaki Y, Ohba K, Toi M, Yamamoto N. Stromal cell-derived factor-1 and CXCR4 receptor interaction in tumor growth and metastasis of breast cancer. Biomed Pharmacother. 2006;60:273–6.CrossRefPubMed

11.

Wu PF, Lu ZP, Cai BB, Tian L, Zou C, Jiang KR, Miao Y. Role of CXCL12/CXCR4 signaling axis in pancreatic cancer. Chin Med J (Engl). 2013;126:3371–4.

12.

Ghanem I, Riveiro ME, Paradis V, Faivre S, de Parga PM, Raymond E. Insights on the CXCL12-CXCR4 axis in hepatocellular carcinoma carcinogenesis. Am J Transl Res. 2014;6:340–52.PubMedPubMedCentral

13.

Rubie C, Kauffels A, Kolsch K, Glanemann M, Justinger C. CXCL12/CXCR4 display an inverse mRNA expression profile in gastric carcinoma that correlates with tumor progression. Oncol Lett. 2016;11:360–4.PubMed

14.

Burns JM, Summers BC, Wang Y, Melikian A, Berahovich R, Miao Z, Penfold ME, Sunshine MJ, Littman DR, Kuo CJ, et al. A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med. 2006;203:2201–13.CrossRefPubMedPubMedCentral

15.

Mazzinghi B, Ronconi E, Lazzeri E, Sagrinati C, Ballerini L, Angelotti ML, Parente E, Mancina R, Netti GS, Becherucci F, et al. Essential but differential role for CXCR4 and CXCR7 in the therapeutic homing of human renal progenitor cells. J Exp Med. 2008;205:479–90.CrossRefPubMedPubMedCentral

16.

Kumar R, Tripathi V, Ahmad M, Nath N, Mir RA, Chauhan SS, Luthra K. CXCR7 mediated Gialpha independent activation of ERK and Akt promotes cell survival and chemotaxis in T cells. Cell Immunol. 2012;272:230–41.CrossRefPubMed

17.

Odemis V, Boosmann K, Heinen A, Kury P, Engele J. CXCR7 is an active component of SDF-1 signalling in astrocytes and Schwann cells. J Cell Sci. 2010;123:1081–8.CrossRefPubMed

18.

Iwakiri S, Mino N, Takahashi T, Sonobe M, Nagai S, Okubo K, Wada H, Date H, Miyahara R. Higher expression of chemokine receptor CXCR7 is linked to early and metastatic recurrence in pathological stage I nonsmall cell lung cancer. Cancer. 2009;115:2580–93.CrossRefPubMed

19.

Marechal R, Demetter P, Nagy N, Berton A, Decaestecker C, Polus M, Closset J, Deviere J, Salmon I, Van Laethem JL. High expression of CXCR4 may predict poor survival in resected pancreatic adenocarcinoma. Br J Cancer. 2009;100:1444–51.CrossRefPubMedPubMedCentral

20.

Long P, Sun F, Ma Y, Huang Y. Inhibition of CXCR4 and CXCR7 for reduction of cell proliferation and invasion in human endometrial cancer. Tumour Biol. 2016;37:7473–80.CrossRefPubMed

21.

Miao Z, Luker KE, Summers BC, Berahovich R, Bhojani MS, Rehemtulla A, Kleer CG, Essner JJ, Nasevicius A, Luker GD, et al. CXCR7 (RDC1) promotes breast and lung tumor growth in vivo and is expressed on tumor-associated vasculature. Proc Natl Acad Sci U S A. 2007;104:15735–40.CrossRefPubMedPubMedCentral

22.

Lee HJ, Jo DY. The role of the CXCR4/CXCL12 axis and its clinical implications in gastric cancer. Histol Histopathol. 2012;27:1155–61.PubMed

23.

Schimanski CC, Galle PR, Moehler M. Chemokine receptor CXCR4-prognostic factor for gastrointestinal tumors. World J Gastroenterol. 2008;14:4721–4.CrossRefPubMedPubMedCentral

24.

Hu L, Duan YT, Li JF, Su LP, Yan M, Zhu ZG, Liu BY, Yang QM. Biglycan enhances gastric cancer invasion by activating FAK signaling pathway. Oncotarget. 2014;5:1885–96.CrossRefPubMedPubMedCentral

25.

Soliman S, Ishrat T, Pillai A, Somanath PR, Ergul A, El-Remessy AB, Fagan SC. Candesartan induces a prolonged proangiogenic effect and augments endothelium-mediated neuroprotection after oxygen and glucose deprivation: role of vascular endothelial growth factors A and B. J Pharmacol Exp Ther. 2014;349:444–57.CrossRefPubMedPubMedCentral

26.

Meijer J, Ogink J, Roos E. Effect of the chemokine receptor CXCR7 on proliferation of carcinoma cells in vitro and in vivo. Br J Cancer. 2008;99:1493–501.CrossRefPubMedPubMedCentral

27.

Wang J, Shiozawa Y, Wang J, Wang Y, Jung Y, Pienta KJ, Mehra R, Loberg R, Taichman RS. The role of CXCR7/RDC1 as a chemokine receptor for CXCL12/SDF-1 in prostate cancer. J Biol Chem. 2008;283:4283–94.CrossRefPubMed

28.

Thelen M, Thelen S. CXCR7, CXCR4 and CXCL12: an eccentric trio? J Neuroimmunol. 2008;198:9–13.CrossRefPubMed

29.

Kalatskaya I, Berchiche YA, Gravel S, Limberg BJ, Rosenbaum JS, Heveker N. AMD3100 is a CXCR7 ligand with allosteric agonist properties. Mol Pharmacol. 2009;75:1240–7.CrossRefPubMed

30.

Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995;1:27–31.CrossRefPubMed

31.

Darash-Yahana M, Pikarsky E, Abramovitch R, Zeira E, Pal B, Karplus R, Beider K, Avniel S, Kasem S, Galun E, Peled A. Role of high expression levels of CXCR4 in tumor growth, vascularization, and metastasis. FASEB J. 2004;18:1240–2.PubMed

Title: SDF-1/CXCR7 axis regulates the proliferation, invasion, adhesion, and angiogenesis of gastric cancer cells
Authors: De-Min Ma
Dian-Xi Luo
Jie Zhang
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: World Journal of Surgical Oncology / Issue 1/2016
Electronic ISSN: 1477-7819
DOI: https://doi.org/10.1186/s12957-016-1009-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

SDF-1/CXCR7 axis regulates the proliferation, invasion, adhesion, and angiogenesis of gastric cancer cells

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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