CXCR7 regulates breast tumor metastasis and angiogenesis in vivo and in vitro

Qian,Tingting; Liu,Yancheng; Dong,Yan; Zhang,Lei; Dong,Yining; Sun,Yanhui; Sun,Dongmei

doi:10.3892/mmr.2017.8286

CXCR7 regulates breast tumor metastasis and angiogenesis in vivo and in vitro

Authors:
- Tingting Qian
- Yancheng Liu
- Yan Dong
- Lei Zhang
- Yining Dong
- Yanhui Sun
- Dongmei Sun
View Affiliations

Affiliations: Laboratory Animal Centre, Bengbu Medical College, Bengbu, Anhui 233000, P.R. China, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, P.R. China, College of Biology and Food Engineering, Chuzhou University, Chuzhou, Anhui 239000, P.R. China, School of Life Sciences and Technology, Tongji University, Shanghai 200092, P.R. China
Published online on: December 15, 2017 https://doi.org/10.3892/mmr.2017.8286
Pages: 3633-3639
Copyright: © Qian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The chemokine receptor CXCR7 is regarded as a scavenger receptor for CXCL12, and induces numerous key steps in tumor growth and metastasis. However, the exact molecular mechanism of CXCR7 regulation in breast tumor angiogenesis remains unknown. In the present study, the function of CXCR7 in breast tumors was investigated in vitro and in vivo. The breast cancer MDA‑MB‑231 cell line was used. Pharmacological inhibition of CXCR7 by CCX771 reduced breast tumor invasion, adhesion and metastasis. Furthermore, CXCR7 was essential for the tube formation of HUVECs in vitro, and for blood vessel formation in a Matrigel plug assay in vivo. In addition, vascular endothelial growth factor expression was also decreased in CCX771‑treated MDA‑MB‑231 cells, indicating that CCX771 regulates tumor angiogenesis. The present results indicated that CXCR7 regulated breast cancer metastasis at multiple stages; additional understanding of CXCR7 in tumor environments may develop anti‑metastatic therapy.

View Figures

View References

1	Ennour-Idrissi K, Maunsell E and Diorio C: Telomere length and breast cancer prognosis: A systematic review. Cancer Epidemiol Biomarkers Prev. 26:3–10. 2017. View Article : Google Scholar : PubMed/NCBI
2	Dhennin-Duthille I, Gautier M, Faouzi M, Guilbert A, Brevet M, Vaudry D, Ahidouch A, Sevestre H and Ouadid-Ahidouch H: High expression of transient receptor potential channels in human breast cancer epithelial cells and tissues: Correlation with pathological parameters. Cell Physiol Biochem. 28:813–822. 2011. View Article : Google Scholar : PubMed/NCBI
3	Pieta B, Chmaj-Wierzchowska K and Opala T: Life style and risk of development of breast and ovarian cancer. Ann Agric Environ Med. 19:379–384. 2012.PubMed/NCBI
4	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
5	Fan L, Strasser-Weippl K, Li JJ, St Louis J, Finkelstein DM, Yu KD, Chen WQ, Shao ZM and Goss PE: Breast cancer in China. Lancet Oncol. 15:e279–e289. 2014. View Article : Google Scholar : PubMed/NCBI
6	Christofori G: Cancer: Division of labour. Nature. 446:735–736. 2007. View Article : Google Scholar : PubMed/NCBI
7	Podsypanina K, Du YC, Jechlinger M, Beverly LJ, Hambardzumyan D and Varmus H: Seeding and propagation of untransformed mouse mammary cells in the lung. Science. 321:1841–1844. 2008. View Article : Google Scholar : PubMed/NCBI
8	Akashi T, Koizumi K, Tsuneyama K, Saiki I, Takano Y and Fuse H: Chemokine receptor CXCR4 expression and prognosis in patients with metastatic prostate cancer. Cancer Sci. 99:539–542. 2008. View Article : Google Scholar : PubMed/NCBI
9	Xu TP, Shen H, Liu LX and Shu YQ: The impact of chemokine receptor CXCR4 on breast cancer prognosis: A meta-analysis. Cancer Epidemiol. 37:725–731. 2013. View Article : Google Scholar : PubMed/NCBI
10	Wald O, Shapira OM and Izhar U: CXCR4/CXCL12 axis in non small cell lung cancer (NSCLC) pathologic roles and therapeutic potential. Theranostics. 3:26–33. 2013. View Article : Google Scholar : PubMed/NCBI
11	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 USA. 104:pp. 15735–15740. 2007; View Article : Google Scholar : PubMed/NCBI
12	Wang J, Shiozawa Y, Wang J, Wang Y, Jung Y, Pienta KJ, Mehra R, Loberg R and Taichman RS: The role of CXCR7/RDC1 as a chemokine receptor for CXCL12/SDF-1 in prostate cancer. J Biol Chem. 283:4283–4294. 2008. View Article : Google Scholar : PubMed/NCBI
13	Marchesi F, Monti P, Leone BE, Zerbi A, Vecchi A, Piemonti L, Mantovani A and Allavena P: Increased survival, proliferation, and migration in metastatic human pancreatic tumor cells expressing functional CXCR4. Cancer Res. 64:8420–8427. 2004. View Article : Google Scholar : PubMed/NCBI
14	Sutton A, Friand V, Brulé-Donneger S, Chaigneau T, Ziol M, Sainte-Catherine O, Poiré A, Saffar L, Kraemer M, Vassy J, et al: Stromal cell-derived factor-1/chemokine (C-X-C motif) ligand 12 stimulates human hepatoma cell growth, migration, and invasion. Mol Cancer Res. 5:21–33. 2007. View Article : Google Scholar : PubMed/NCBI
15	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. 203:2201–2213. 2006. View Article : Google Scholar : PubMed/NCBI
16	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. 205:479–490. 2008. View Article : Google Scholar : PubMed/NCBI
17	Perlin JR and Talbot WS: Signals on the move: Chemokine receptors and organogenesis in zebrafish. Sci STKE. 2007:pe452007. View Article : Google Scholar : PubMed/NCBI
18	Gerrits H, van Ingen Schenau DS, Bakker NE, van Disseldorp AJ, Strik A, Hermens LS, Koenen TB, Krajnc-Franken MA and Gossen JA: Early postnatal lethality and cardiovascular defects in CXCR7-deficient mice. Genesis. 46:235–245. 2008. View Article : Google Scholar : PubMed/NCBI
19	Li Q, Zhang A, Tao C, Li X and Jin P: The role of SDF-1-CXCR4/CXCR7 axis in biological behaviors of adipose tissue-derived mesenchymal stem cells in vitro. Biochem Biophys Res Commun. 441:675–680. 2013. View Article : Google Scholar : PubMed/NCBI
20	Zheng K, Li HY, Su XL, Wang XY, Tian T, Li F and Ren GS: Chemokine receptor CXCR7 regulates the invasion, angiogenesis and tumor growth of human hepatocellular carcinoma cells. J Exp Clin Cancer Res. 29:312010. View Article : Google Scholar : PubMed/NCBI
21	Singh RK and Lokeshwar BL: The IL-8-regulated chemokine receptor CXCR7 stimulates EGFR signaling to promote prostate cancer growth. Cancer Res. 71:3268–3277. 2011. View Article : Google Scholar : PubMed/NCBI
22	Hao M, Zheng J, Hou K and Wang J, Chen X, Lu X, Bo J, Xu C, Shen K and Wang J: Role of chemokine receptor CXCR7 in bladder cancer progression. Biochem Pharmacol. 84:204–214. 2012. View Article : Google Scholar : PubMed/NCBI
23	Xue TC, Chen RX, Han D, Chen J, Xue Q, Gao DM, Sun RX, Tang ZY and Ye SL: Down-regulation of CXCR7 inhibits the growth and lung metastasis of human hepatocellular carcinoma cells with highly metastatic potential. Exp Ther Med. 3:117–123. 2012. View Article : Google Scholar : PubMed/NCBI
24	Kollmar O, Rupertus K, Scheuer C, Nickels RM, Haberl GC, Tilton B, Menger MD and Schilling MK: CXCR4 and CXCR7 regulate angiogenesis and CT26.WT tumor growth independent from SDF-1. Int J Cancer. 126:1302–1315. 2010.PubMed/NCBI
25	Bauerle KT, Schweppe RE, Lund G, Kotnis G, Deep G, Agarwal R, Pozdeyev N, Wood WM and Haugen BR: Nuclear factor κB-dependent regulation of angiogenesis, and metastasis in an in vivo model of thyroid cancer is associated with secreted interleukin-8. J Clin Endocrinol Metab. 99:E1436–E1444. 2014. View Article : Google Scholar : PubMed/NCBI
26	Qin Y, Zhou Z, Zhang F, Wang Y, Shen B, Liu Y, Guo Y, Fan Y and Qiu J: Induction of regulatory B-cells by mesenchymal stem cells is affected by SDF-1α-CXCR7. Cell Physiol Biochem. 37:117–130. 2015. View Article : Google Scholar : PubMed/NCBI
27	Zhou SM, Zhang F, Chen XB, Jun CM, Jing X, Wei DX, Xia Y, Zhou YB, Xiao XQ, Jia RQ, et al: miR-100 suppresses the proliferation and tumor growth of esophageal squamous cancer cells via targeting CXCR7. Oncol Rep. 35:3453–3459. 2016. View Article : Google Scholar : PubMed/NCBI
28	Inaguma S, Riku M, Ito H, Tsunoda T, Ikeda H and Kasai K: GLI1 orchestrates CXCR4/CXCR7 signaling to enhance migration and metastasis of breast cancer cells. Oncotarget. 6:33648–33657. 2015. View Article : Google Scholar : PubMed/NCBI
29	Young B, Purcell C, Kuang YQ, Charette N and Dupré DJ: Superoxide dismutase 1 regulation of CXCR4-mediated signaling in prostate cancer cells is dependent on cellular oxidative state. Cell Physiol Biochem. 37:2071–2084. 2015. View Article : Google Scholar : PubMed/NCBI
30	Zhang S, Wang Y, Chen M, Sun L, Han J, Elena VK and Qiao H: CXCL12 methylation-mediated epigenetic regulation of gene expression in papillary thyroid carcinoma. Sci Rep. 7:440332017. View Article : Google Scholar : PubMed/NCBI
31	Chen Y, Teng F, Wang G and Nie Z: Overexpression of CXCR7 induces angiogenic capacity of human hepatocellular carcinoma cells via the AKT signaling pathway. Oncol Rep. 36:2275–2281. 2016. View Article : Google Scholar : PubMed/NCBI
32	Guo JC, Li J, Zhou L, Yang JY, Zhang ZG, Liang ZY, Zhou WX, You L, Zhang TP and Zhao YP: CXCL12-CXCR7 axis contributes to the invasive phenotype of pancreatic cancer. Oncotarget. 7:62006–62018. 2016. View Article : Google Scholar : PubMed/NCBI
33	Wurth R, Barbieri F, Bajetto A, Pattarozzi A, Gatti M, Porcile C, Zona G, Ravetti JL, Spaziante R and Florio T: Expression of CXCR7 chemokine receptor in human meningioma cells and in intratumoral microvasculature. J Neuroimmunol. 234:115–123. 2011. View Article : Google Scholar : PubMed/NCBI
34	Totonchy JE, Osborn JM, Botto S, Clepper L and Moses AV: Aberrant proliferation in CXCR7+ endothelial cells via degradation of the retinoblastoma protein. PloS One. 8:e698282013. View Article : Google Scholar : PubMed/NCBI
35	Barbieri F, Thellung S, Würth R, Gatto F, Corsaro A, Villa V, Nizzari M, Albertelli M, Ferone D and Florio T: Emerging targets in pituitary adenomas: Role of the CXCL12/CXCR4-R7 System. Int J Endocrinol. 2014:7535242014. View Article : Google Scholar : PubMed/NCBI