High expression of CXCR4, CXCR7 and SDF-1 predicts poor survival in renal cell carcinoma

World Journal of Surgical Oncology - 2012
Linhui Wang1, Wei Chen1, Li Gao2, Qing Yang1, Bing Liu1, Zhenjie Wu1, Yang Wang2, Ying-hao Sun1
1The Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai, China
2The Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China

Tóm tắt

Abstract Background Chemokines and their receptors are known to play important roles in the tumorigenesis of many malignancies. The aim of this study was to evaluate the prognostic impact of the expression of the chemokine SDF-1 and its receptors CXCR4 and CXCR7 in patients with renal cell carcinoma. Methods The expression of CXCR4, CXCR7 and SDF-1 in specimens from 97 renal cell carcinoma patients was evaluated by immunohistochemistry on a tissue microarray. These results were correlated with the clinicopathological parameters and survival of the patients. Results CXCR4 and CXCR7 were expressed in all patients, whereas SDF-1 was expressed in 61 patients (62.9%). No association was observed between the expression of CXCR4, CXCR7 or SDF-1 and the clinical or pathological data except between SDF-1 expression and Fuhrman’s grade (P = 0.015). Patients with high expression of CXCR4, CXCR7 and SDF-1 had shorter overall survival and recurrence-free survival than those with low expression. In a multivariate analysis, the high expression of CXCR4, CXCR7 and SDF-1 correlated with poor overall survival and recurrence-free survival independent of gender, age, AJCC stage, lymph node status, metastasis, histologic variant and Fuhrman’s grade. Conclusions High levels of CXCR4, CXCR7 and SDF-1 were associated with poor overall survival and recurrence-free survival in renal cell carcinoma patients. CXCR4, CXCR7 and SDF-1 may serve as useful prognostic markers and therapeutic targets for renal cell carcinoma.

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Tài liệu tham khảo

Jones J, Libermann TA: Genomics of renal cell cancer: the biology behind and the therapy ahead. Clin Cancer Res. 2007, 13: 685s-692s. 10.1158/1078-0432.CCR-06-1867.

Pantuck AJ, Zisman A, Dorey F, Chao DH, Han KR, Said J, Gitlitz B, Belldegrun AS, Figlin RA: Renal cell carcinoma with retroperitoneal lymph nodes. Impact on survival and benefits of immunotherapy. Cancer. 2003, 97: 2995-3002. 10.1002/cncr.11422.

Müller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verástegui E, Zlotnik A: Involvement of chemokine receptors in breast cancer metastasis. Nature. 2001, 410: 50-56. 10.1038/35065016.

Lazennec G, Richmond A: Chemokines and chemokine receptors: new insights into cancer-related inflammation. Trends Mol Med. 2010, 16: 133-144. 10.1016/j.molmed.2010.01.003.

Zlotnik A, Yoshie O: Chemokines: a new classification system and their role in immunity. Immunity. 2000, 12: 121-127. 10.1016/S1074-7613(00)80165-X.

Murphy PM, Baggiolini M, Charo IF, Hébert CA, Horuk R, Matsushima K, Miller LH, Oppenheim JJ, Power CA: International union of pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacol Rev. 2000, 52: 145-176.

Schimanski CC, Galle PR, Moehler M: Chemokine receptor CXCR4-prognostic factor for gastrointestinal tumors. World J Gastroenterol. 2008, 14: 4721-4724. 10.3748/wjg.14.4721.

Matsusue R, Kubo H, Hisamori S, Okoshi K, Takagi H, Hida K, Nakano K, Itami A, Kawada K, Nagayama S, Sakai Y: Hepatic stellate cells promote liver metastasis of colon cancer cells by the action of SDF-1/CXCR4 axis. Ann Surg Oncol. 2009, 16: 2645-2653. 10.1245/s10434-009-0599-x.

Burns JM, Summers BC, Wang Y, Melikian A, Berahovich R, Miao Z, Penfold ME, Sunshine MJ, Littman DR, Kuo CJ, Wei K, McMaster BE, Wright K, Howard MC, Schall TJ: A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med. 2006, 203: 2201-2213. 10.1084/jem.20052144.

Miao Z, Luker KE, Summers BC, Berahovich R, Bhojani MS, Rehemtulla A, Kleer CG, Essner JJ, Nasevicius A, Luker GD, Howard MC, Schall TJ: 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: 15735-15740. 10.1073/pnas.0610444104.

Hattermann K, Held-Feindt J, Lucius R, Müerköster SS, Penfold ME, Schall TJ, Mentlein R: The chemokine receptor CXCR7 is highly expressed in human glioma cells and mediates antiapoptotic effects. Cancer Res. 2010, 70: 3299-3308. 10.1158/0008-5472.CAN-09-3642.

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: 4283-4294.

Zagzag D, Krishnamachary B, Yee H, Okuyama H, Chiriboga L, Ali MA, Melamed J, Semenza GL: Stromal cell-derived factor-1alpha and CXCR4 expression in hemangioblastoma and clear cell-renal cell carcinoma: von Hippel-Lindau loss-of-function induces expression of a ligand and its receptor. Cancer Res. 2005, 65: 6178-6188. 10.1158/0008-5472.CAN-04-4406.

Li Q, Bavikatty N, Michael CW: The role of immunohistochemistry in distinguishing squamous cell carcinoma from mesothelioma and adenocarcinoma in pleural effusion. Semin Diagn Pathol. 2006, 23: 15-19. 10.1053/j.semdp.2006.06.007.

Woo SU, Bae JW, Kim CH, Lee JB, Koo BW: A significant correlation between nuclear CXCR4 expression and axillary lymph node metastasis in hormonal receptor negative breast cancer. Ann Surg Oncol. 2008, 15: 281-285. 10.1245/s10434-007-9595-1.

Na IK, Scheibenbogen C, Adam C, Stroux A, Ghadjar P, Thiel E, Keilholz U, Coupland SE: Nuclear expression of CXCR4 in tumor cells of non-small cell lung cancer is correlated with lymph node metastasis. Hum Pathol. 2008, 39: 1751-1755. 10.1016/j.humpath.2008.04.017.

Wang L, Wang Z, Yang B, Yang Q, Wang L, Sun Y: CXCR4 nuclear localization follows binding of its ligand SDF-1 and occurs in metastatic but not primary renal cell carcinoma. Oncol Rep. 2009, 22: 1333-1339.

D’Alterio C, Consales C, Polimeno M, Franco R, Cindolo L, Portella L, Cioffi M, Calemma R, Marra L, Claudio L, Perdonà S, Pignata S, Facchini G, Cartenì G, Longo N, Pucci L, Ottaiano A, Costantini S, Castello G, Scala S: Concomitant CXCR4 and CXCR7 expression predicts poor prognosis in renal cancer. Curr Cancer Drug Targets. 2010, 10: 772-781. 10.2174/156800910793605839.

Hou KL, Hao MG, Bo JJ, Wang JH: CXCR7 in tumorigenesis and progression. Chin J Cancer. 2010, 29: 456-459. 10.5732/cjc.009.10404.

Thelen M, Thelen S: CXCR7, CXCR4 and CXCL12: an eccentric trio?. J Neuroimmunol. 2008, 198: 9-13. 10.1016/j.jneuroim.2008.04.020.

Levoye A, Balabanian K, Baleux F, Bachelerie F, Lagane B: CXCR7 heterodimerizes with CXCR4 and regulates CXCL12-mediated G protein signaling. Blood. 2009, 113: 6085-6093. 10.1182/blood-2008-12-196618.

Liang JJ, Zhu S, Bruggeman R, Zaino RJ, Evans DB, Fleming JB, Gomez HF, Zander DS, Wang H: High levels of expression of human stromal cell-derived factor-1 are associated with worse prognosis in patients with stage II pancreatic ductal adenocarcinoma. Cancer Epidemiol Biomarkers Prev. 2010, 19: 2598-2604. 10.1158/1055-9965.EPI-10-0405.

Gebauer F, Tachezy M, Effenberger K, von Loga K, Zander H, Marx A, Kaifi JT, Sauter G, Izbicki JR, Bockhorn M: Prognostic impact of CXCR4 and CXCR7 expression in pancreatic adenocarcinoma. J Surg Oncol. 2011, 104: 140-145. 10.1002/jso.21957.

Rubin JB, Kung AL, Klein RS, Chan JA, Sun Y, Schmidt K, Kieran MW, Luster AD, Segal RA: A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors. Proc Natl Acad Sci U S A. 2003, 100: 13513-13518. 10.1073/pnas.2235846100.

Smith MC, Luker KE, Garbow JR, Prior JL, Jackson E, Piwnica-Worms D, Luker GD: CXCR4 regulates growth of both primary and metastatic breast cancer. Cancer Res. 2004, 64: 8604-8612. 10.1158/0008-5472.CAN-04-1844.

Burger JA, Stewart DJ: CXCR4 chemokine receptor antagonists: perspectives in SCLC. Expert Opin Investig Drugs. 2009, 18: 481-490. 10.1517/13543780902804249.

Hartmann TN, Grabovsky V, Pasvolsky R, Shulman Z, Buss EC, Spiegel A, Nagler A, Lapidot T, Thelen M, Alon R: A crosstalk between intracellular CXCR7 and CXCR4 involved in rapid CXCL12-triggered integrin activation but not in chemokine-triggered motility of human T lymphocytes and CD34+ cells. J Leukoc Biol. 2008, 84: 1130-1140. 10.1189/jlb.0208088.

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World Journal of Surgical Oncology

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