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Erschienen in: Archives of Gynecology and Obstetrics 4/2017

27.02.2017 | Gynecologic Oncology

The role of the SDF-1/ CXCR7 axis on the growth and invasion ability of endometrial cancer cells

verfasst von: Hong-qin Gu, Zhen-bo Zhang, Jia-wen Zhang, Qian-qian Wang, Xiao-wei Xi, Yin-yan He

Erschienen in: Archives of Gynecology and Obstetrics | Ausgabe 4/2017

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Abstract

Purpose

Stroma-derived factor-1 (SDF-1) and its receptor C-X-C chemokine receptor-4 (CXCR4) are involved in human endometrial carcinoma (EC) progression. CXCR7 is another important receptor of SDF-1 and has a higher affinity with SDF-1 compared with that of CXCR4. This paper aims to study the effects of the SDF-1/CXCR7 axis on the growth and invasion ability of EC cells.

Methods

CXCR7 expression was evaluated by quantitative RT-PCR, immunohistochemistry, immunocytochemistry and Western blotting in EC cell lines and 30 cases of primary EC tissue from patients. EC cell line proliferation and migration were assessed following knockdown of CXCR7 by MTT and transwell assays.

Results

The results showed that CXCR7 was highly expressed at both mRNA and protein levels in the EC cells and tissue. siCXCR7 effectively silenced CXCR7 in Ishikawa and AN3CA cells. Treatment with 17β-oestradiol (17β-E2) significantly increased the levels of CXCR7 and SDF-1 in Con, siCon and siCXCR7 treated Ishikawa. siCXCR7 persistently inhibited CXCR7 expression, even in cells treated with 17β-E2. Moreover, in vitro functional analyses, silencing CXCR7 resulted in decreased proliferation in Ishikawa and AN3CA cells. Treatment with 17β-E2 and SDF-1 significantly promoted the growth and migration in siCon treated Ishikawa and AN3CA. Interestingly, in response to 17β-E2 and SDF-1 stimulation, siCXCR7 continuously inhibited the growth and invasion of Ishikawa and AN3CA cells.

Conclusion

Our results indicate that SDF-1/CXCR7 plays a positive role in the proliferation and invasion of EC cells. CXCR7 inhibition treatment may provide a promising strategy for anti-tumour therapy for EC.
Literatur
1.
Zurück zum Zitat Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90CrossRefPubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90CrossRefPubMed
2.
Zurück zum Zitat Rasool N, Fader AN, Seamon L, Neubauer NL, Shahin FA, Alexander HA et al (2010) Grade 3 endometrioid adenocarcinoma of the endometrium: an analysis of clinical outcomes and patterns of recurrence. Gynecol Oncol 116:10–14CrossRefPubMed Rasool N, Fader AN, Seamon L, Neubauer NL, Shahin FA, Alexander HA et al (2010) Grade 3 endometrioid adenocarcinoma of the endometrium: an analysis of clinical outcomes and patterns of recurrence. Gynecol Oncol 116:10–14CrossRefPubMed
3.
Zurück zum Zitat Rabinovich A (2016) Neo-adjuvant chemotherapy for advanced stage endometrial carcinoma: a glimmer of hope in select patients. Arch Gynecol Obstet 293:47–53CrossRefPubMed Rabinovich A (2016) Neo-adjuvant chemotherapy for advanced stage endometrial carcinoma: a glimmer of hope in select patients. Arch Gynecol Obstet 293:47–53CrossRefPubMed
5.
Zurück zum Zitat Chen N, Jiang X, Wang J, Wu T, Cheng B, Xia J (2016) CXCL12-CXCR4/CXCR7 axis contributes to cell motilities of oral squamous cell carcinoma. Tumour Biol 37:567–575CrossRefPubMed Chen N, Jiang X, Wang J, Wu T, Cheng B, Xia J (2016) CXCL12-CXCR4/CXCR7 axis contributes to cell motilities of oral squamous cell carcinoma. Tumour Biol 37:567–575CrossRefPubMed
6.
Zurück zum Zitat Teicher BA, Fricker SP (2010) CXCL12 (SDF-1)/CXCR4 pathway in cancer. Clin Cancer Res 16:2927–2931CrossRefPubMed Teicher BA, Fricker SP (2010) CXCL12 (SDF-1)/CXCR4 pathway in cancer. Clin Cancer Res 16:2927–2931CrossRefPubMed
7.
Zurück zum Zitat Liao YX, Zhou CH, Zeng H, Zuo DQ, Wang ZY, Yin F et al (2013) The role of the CXCL12- CXCR4/ CXCR7 axis in the progression and metastasis of bone sarcomas (review). Int J Mol Med 32:1239–1246PubMed Liao YX, Zhou CH, Zeng H, Zuo DQ, Wang ZY, Yin F et al (2013) The role of the CXCL12- CXCR4/ CXCR7 axis in the progression and metastasis of bone sarcomas (review). Int J Mol Med 32:1239–1246PubMed
8.
Zurück zum Zitat Hattermann K, Mentlein R (2013) An infernal trio: the chemokine CXCL12 and its receptors CXCR4 and CXCR7 in tumor biology. Ann Anat 195:103–110CrossRefPubMed Hattermann K, Mentlein R (2013) An infernal trio: the chemokine CXCL12 and its receptors CXCR4 and CXCR7 in tumor biology. Ann Anat 195:103–110CrossRefPubMed
9.
Zurück zum Zitat Burns JM, Summers BC, Wang Y, Melikian A, Berahovich R, Miao Z et al (2006) A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med 203:2201–2213CrossRefPubMedPubMedCentral Burns JM, Summers BC, Wang Y, Melikian A, Berahovich R, Miao Z et al (2006) A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med 203:2201–2213CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Wang J, Shiozawa Y, Wang J, Wang Y, Jung Y, Pienta KJ et al (2008) The role of CXCR7/RDC1 as a chemokine receptor for CXCL12/SDF-1 in prostate cancer. J Biol Chem 283:4283–4294CrossRefPubMed Wang J, Shiozawa Y, Wang J, Wang Y, Jung Y, Pienta KJ et al (2008) The role of CXCR7/RDC1 as a chemokine receptor for CXCL12/SDF-1 in prostate cancer. J Biol Chem 283:4283–4294CrossRefPubMed
11.
Zurück zum Zitat Salazar N, Muñoz D, Kallifatidis G, Singh RK, Jordà M, Lokeshwar BL (2014) The chemokine receptor CXCR7 interacts with EGFR to promote breast cancer cell proliferation. Mol Cancer 13:198CrossRefPubMedPubMedCentral Salazar N, Muñoz D, Kallifatidis G, Singh RK, Jordà M, Lokeshwar BL (2014) The chemokine receptor CXCR7 interacts with EGFR to promote breast cancer cell proliferation. Mol Cancer 13:198CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Tsukamoto H, Shibata K, Kajiyama H, Terauchi M, Nawa A, Kikkawa F (2007) Uterine smooth muscle cells increase invasive ability of endometrial carcinoma cells through tumor-stromal interaction. Clin Exp Metastasis 24:423–429CrossRefPubMed Tsukamoto H, Shibata K, Kajiyama H, Terauchi M, Nawa A, Kikkawa F (2007) Uterine smooth muscle cells increase invasive ability of endometrial carcinoma cells through tumor-stromal interaction. Clin Exp Metastasis 24:423–429CrossRefPubMed
13.
Zurück zum Zitat Miao Z, Luker KE, Summers BC, Berahovich R, Bhojani MS, Rehemtulla A et al (2007) CXCR7 (RDC1) promotes breast and lung tumor growth in vivo and is expressed on tumor-associated vasculature. Proc Natl Acad Sci USA 104:15735–15740CrossRefPubMedPubMedCentral Miao Z, Luker KE, Summers BC, Berahovich R, Bhojani MS, Rehemtulla A et al (2007) CXCR7 (RDC1) promotes breast and lung tumor growth in vivo and is expressed on tumor-associated vasculature. Proc Natl Acad Sci USA 104:15735–15740CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Yang DL, Xin MM, Wang JS, Xu HY, Huo Q, Tang ZR et al (2015) Chemokine receptor CXCR4 and its ligand CXCL12 expressions and clinical significance in bladder cancer. Genet Mol Res 14:17699–17707CrossRefPubMed Yang DL, Xin MM, Wang JS, Xu HY, Huo Q, Tang ZR et al (2015) Chemokine receptor CXCR4 and its ligand CXCL12 expressions and clinical significance in bladder cancer. Genet Mol Res 14:17699–17707CrossRefPubMed
15.
Zurück zum Zitat Smolkova B, Mego M, Horvathova Kajabova V, Cierna Z, Danihel L, Sedlackova T et al (2016) Expression of SOCS1 and CXCL12 proteins in primary breast cancer are associated with presence of circulating tumor cells in peripheral blood. Transl Oncol 9:184–190 Smolkova B, Mego M, Horvathova Kajabova V, Cierna Z, Danihel L, Sedlackova T et al (2016) Expression of SOCS1 and CXCL12 proteins in primary breast cancer are associated with presence of circulating tumor cells in peripheral blood. Transl Oncol 9:184–190
16.
Zurück zum Zitat Yang D, Dai T, Xue L, Liu X, Wu B, Geng J et al (2015) Expression of chemokine receptor CXCR7 in colorectal carcinoma and its prognostic significance. Int J Clin Exp Pathol 8:13051–13058PubMedPubMedCentral Yang D, Dai T, Xue L, Liu X, Wu B, Geng J et al (2015) Expression of chemokine receptor CXCR7 in colorectal carcinoma and its prognostic significance. Int J Clin Exp Pathol 8:13051–13058PubMedPubMedCentral
17.
Zurück zum Zitat Zhu L, Luo K, Gu XH, Hou N, Huang CP, Lou Q et al (2015) CXCR7 expression in nasopharyngeal carcinoma tissues correlates with disease severity. Int J Clin Exp Med 8:21257–21261PubMedPubMedCentral Zhu L, Luo K, Gu XH, Hou N, Huang CP, Lou Q et al (2015) CXCR7 expression in nasopharyngeal carcinoma tissues correlates with disease severity. Int J Clin Exp Med 8:21257–21261PubMedPubMedCentral
18.
Zurück zum Zitat Walentowicz-Sadlecka M, Sadlecki P, Bodnar M, Marszalek A, Walentowicz P, Sokup A et al (2014) Stromal derived factor-1 (SDF-1) and its receptors CXCR4 and CXCR7 in endometrial cancer patients. PLoS One 9:e84629CrossRefPubMedPubMedCentral Walentowicz-Sadlecka M, Sadlecki P, Bodnar M, Marszalek A, Walentowicz P, Sokup A et al (2014) Stromal derived factor-1 (SDF-1) and its receptors CXCR4 and CXCR7 in endometrial cancer patients. PLoS One 9:e84629CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Wan L, Zou Y, Wan LH, Wang LQ, Huang MZ, Wu J et al (2015) Tanshinone IIA inhibits the proliferation, migration and invasion of ectopic endometrial stromal cells of adenomyosis via 14-3-3ζ downregulation. Arch Gynecol Obstet 292:1301–1309CrossRefPubMed Wan L, Zou Y, Wan LH, Wang LQ, Huang MZ, Wu J et al (2015) Tanshinone IIA inhibits the proliferation, migration and invasion of ectopic endometrial stromal cells of adenomyosis via 14-3-3ζ downregulation. Arch Gynecol Obstet 292:1301–1309CrossRefPubMed
20.
Zurück zum Zitat Naumann U, Cameroni E, Pruenster M, Mahabaleshwar H, Raz E, Zerwes HG et al (2010) CXCR7 functions as a scavenger for CXCL12 and CXCL11. PLoS One 5:e9175CrossRefPubMedPubMedCentral Naumann U, Cameroni E, Pruenster M, Mahabaleshwar H, Raz E, Zerwes HG et al (2010) CXCR7 functions as a scavenger for CXCL12 and CXCL11. PLoS One 5:e9175CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Maksym RB, Tarnowski M, Grymula K, Tarnowska J, Wysoczynski M, Liu R et al (2009) The role of stromal-derived factor-1–CXCR7 axis in development and cancer. Eur J Pharmacol 625:31–40CrossRefPubMedPubMedCentral Maksym RB, Tarnowski M, Grymula K, Tarnowska J, Wysoczynski M, Liu R et al (2009) The role of stromal-derived factor-1–CXCR7 axis in development and cancer. Eur J Pharmacol 625:31–40CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Liu P, Long P, Huang Y, Sun F, Wang Z (2016) CXCL12/CXCR4 axis induces proliferation and invasion in human endometrial cancer. Am J Trans Res 8:1719–1729 Liu P, Long P, Huang Y, Sun F, Wang Z (2016) CXCL12/CXCR4 axis induces proliferation and invasion in human endometrial cancer. Am J Trans Res 8:1719–1729
23.
Zurück zum Zitat Gelmini S, Mangoni M, Castiglione F, Beltrami C, Pieralli A, Andersson KL et al (2009) The CXCR4/CXCL12 axis in endometrial cancer. Clin Exp Metastasis 26:261–268CrossRefPubMed Gelmini S, Mangoni M, Castiglione F, Beltrami C, Pieralli A, Andersson KL et al (2009) The CXCR4/CXCL12 axis in endometrial cancer. Clin Exp Metastasis 26:261–268CrossRefPubMed
24.
Zurück zum Zitat Sun H, Wang X, Zhang Y, Che X, Liu Z, Zhang L et al (2016) Biglycan enhances the ability of migration and invasion in endometrial cancer. Arch Gynecol Obstet 293:429–438CrossRefPubMed Sun H, Wang X, Zhang Y, Che X, Liu Z, Zhang L et al (2016) Biglycan enhances the ability of migration and invasion in endometrial cancer. Arch Gynecol Obstet 293:429–438CrossRefPubMed
25.
Zurück zum Zitat Wormke M, Castro-Rivera E, Chen I, Safe S (2000) Estrogen and aryl hydrocarbon receptor expression and crosstalk in human Ishikawa endometrial cancer cells. J Steroid Biochem Mol Biol 72:197–207CrossRefPubMed Wormke M, Castro-Rivera E, Chen I, Safe S (2000) Estrogen and aryl hydrocarbon receptor expression and crosstalk in human Ishikawa endometrial cancer cells. J Steroid Biochem Mol Biol 72:197–207CrossRefPubMed
26.
Zurück zum Zitat Gehrig PA, Bae-Jump VL (2010) Promising novel therapies for the treatment of endometrial cancer. Gynecol Oncol 116:187–194CrossRefPubMed Gehrig PA, Bae-Jump VL (2010) Promising novel therapies for the treatment of endometrial cancer. Gynecol Oncol 116:187–194CrossRefPubMed
27.
Zurück zum Zitat Attar R, Agachan B, Kuran SB, Cacina C, Sozen S, Yurdum LM et al (2010) Association of CCL2 and CCR2 gene variants with endometrial cancer in Turkish women. In Vivo 24:243–248PubMed Attar R, Agachan B, Kuran SB, Cacina C, Sozen S, Yurdum LM et al (2010) Association of CCL2 and CCR2 gene variants with endometrial cancer in Turkish women. In Vivo 24:243–248PubMed
28.
Zurück zum Zitat Sauvé K, Lepage J, Sanchez M, Heveker N, Tremblay A (2009) Positive feedback activation of estrogen receptors by the CXCL12-CXCR4 pathway. Cancer Res 69:5793–5800CrossRefPubMed Sauvé K, Lepage J, Sanchez M, Heveker N, Tremblay A (2009) Positive feedback activation of estrogen receptors by the CXCL12-CXCR4 pathway. Cancer Res 69:5793–5800CrossRefPubMed
29.
Zurück zum Zitat Yan X, Cai S, Xiong X, Sun W, Dai X, Chen S et al (2012) Chemokine receptor CXCR7 mediates human endothelial progenitor cells survival, angiogenesis, but not proliferation. J Cell Biochem 113:1437–1446CrossRefPubMed Yan X, Cai S, Xiong X, Sun W, Dai X, Chen S et al (2012) Chemokine receptor CXCR7 mediates human endothelial progenitor cells survival, angiogenesis, but not proliferation. J Cell Biochem 113:1437–1446CrossRefPubMed
30.
Zurück zum Zitat Zabel BA, Lewén S, Berahovich RD, Jaén JC, Schall TJ (2011) The novel chemokine receptor CXCR7 regulates trans-endothelial migration of cancer cells. Mol Cancer 10:73CrossRefPubMedPubMedCentral Zabel BA, Lewén S, Berahovich RD, Jaén JC, Schall TJ (2011) The novel chemokine receptor CXCR7 regulates trans-endothelial migration of cancer cells. Mol Cancer 10:73CrossRefPubMedPubMedCentral
Metadaten
Titel
The role of the SDF-1/ CXCR7 axis on the growth and invasion ability of endometrial cancer cells
verfasst von
Hong-qin Gu
Zhen-bo Zhang
Jia-wen Zhang
Qian-qian Wang
Xiao-wei Xi
Yin-yan He
Publikationsdatum
27.02.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Archives of Gynecology and Obstetrics / Ausgabe 4/2017
Print ISSN: 0932-0067
Elektronische ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-017-4308-x

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