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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 1/2014

Open Access 01-05-2014 | Preclinical Study

C–X–C ligand 10 and C–X–C receptor 3 status can predict tamoxifen treatment response in breast cancer patients

Authors: Erik Hilborn, Tove Sivik, Tommy Fornander, Olle Stål, Bo Nordenskjöld, Agneta Jansson

Published in: Breast Cancer Research and Treatment | Issue 1/2014

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Abstract

To investigate the expression levels of CXCL10 and CXCR3 in tumors from breast cancer patients randomized to adjuvant tamoxifen treatment or no endocrine treatment, in order to further study the connection to prognosis and prediction of tamoxifen treatment outcome. Immunohistochemistry on tissue microarrays from 912 breast cancer patients randomized to tamoxifen or no endocrine treatment. CXCR3 status was found to be a prognostic tool in predicting distant recurrence, as well as reduced breast cancer-specific survival. In patients with estrogen receptor (ER)-positive tumors, tumors with strong CXCL10 levels had improved effect of tamoxifen treatment in terms of local recurrence-free survival [risk ratio (RR) 0.46 (95 % CI 0.25–0.85, P = 0.01)] compared with patients with tumors expressing weak CXCL10 expression. Further, patients with ER-positive tumors with strong CXCR3 expression had an improved effect of tamoxifen in terms of breast cancer-specific survival [RR 0.34 (95 % CI 0.19–0.62, P < 0.001)] compared with the group with weak CXCR3 levels [RR 1.33 (95 % CI 0.38–4.79, P = 0.65)]. We show here for the first time that CXCL10 and CXCR3 expression are both predictors of favorable outcome in patients treated with tamoxifen.
Literature
1.
2.
Kajitani K, Tanaka Y, Arihiro K, Kataoka T, Ohdan H (2012) Mechanistic analysis of the antitumor efficacy of human natural killer cells against breast cancer cells. Breast Cancer Res Treat 134(1):139–155. doi:10.​1007/​s10549-011-1944-x CrossRefPubMed
3.
Luster AD, Leder P (1993) IP-10, a –C–X–C– chemokine, elicits a potent thymus-dependent antitumor response in vivo. J Exp Med 178(3):1057–1065CrossRefPubMed
4.
Taub DD, Lloyd AR, Conlon K, Wang JM, Ortaldo JR, Harada A, Matsushima K, Kelvin DJ, Oppenheim JJ (1993) Recombinant human interferon-inducible protein 10 is a chemoattractant for human monocytes and T lymphocytes and promotes T cell adhesion to endothelial cells. J Exp Med 177(6):1809–1814CrossRefPubMed
5.
Cole KE, Strick CA, Paradis TJ, Ogborne KT, Loetscher M, Gladue RP, Lin W, Boyd JG, Moser B, Wood DE, Sahagan BG, Neote K (1998) Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3. J Exp Med 187(12):2009–2021PubMedCentralCrossRefPubMed
6.
Arenberg DA, Kunkel SL, Polverini PJ, Morris SB, Burdick MD, Glass MC, Taub DT, Iannettoni MD, Whyte RI, Strieter RM (1996) Interferon-gamma-inducible protein 10 (IP-10) is an angiostatic factor that inhibits human non-small cell lung cancer (NSCLC) tumorigenesis and spontaneous metastases. J Exp Med 184(3):981–992CrossRefPubMed
7.
Giuliani N, Bonomini S, Romagnani P, Lazzaretti M, Morandi F, Colla S, Tagliaferri S, Lasagni L, Annunziato F, Crugnola M, Rizzoli V (2006) CXCR3 and its binding chemokines in myeloma cells: expression of isoforms and potential relationships with myeloma cell proliferation and survival. Haematologica 91(11):1489–1497PubMed
8.
Goldberg-Bittman L, Neumark E, Sagi-Assif O, Azenshtein E, Meshel T, Witz IP, Ben-Baruch A (2004) The expression of the chemokine receptor CXCR3 and its ligand, CXCL10, in human breast adenocarcinoma cell lines. Immunol Lett 92(1–2):171–178CrossRefPubMed
9.
Lo BK, Yu M, Zloty D, Cowan B, Shapiro J, McElwee KJ (2010) CXCR3/ligands are significantly involved in the tumorigenesis of basal cell carcinomas. Am J Pathol 176(5):2435–2446PubMedCentralCrossRefPubMed
10.
Zipin-Roitman A, Meshel T, Sagi-Assif O, Shalmon B, Avivi C, Pfeffer RM, Witz IP, Ben-Baruch A (2007) CXCL10 promotes invasion-related properties in human colorectal carcinoma cells. Cancer Res 67(7):3396–3405CrossRefPubMed
11.
Persano L, Moserle L, Esposito G, Bronte V, Barbieri V, Iafrate M, Gardiman MP, Larghero P, Pfeffer U, Naschberger E, Sturzl M, Indraccolo S, Amadori A (2009) Interferon-alpha counteracts the angiogenic switch and reduces tumor cell proliferation in a spontaneous model of prostatic cancer. Carcinogenesis 30(5):851–860CrossRefPubMed
12.
Dorsey R, Kundu N, Yang Q, Tannenbaum CS, Sun H, Hamilton TA, Fulton AM (2002) Immunotherapy with interleukin-10 depends on the CXC chemokines inducible protein-10 and monokine induced by IFN-gamma. Cancer Res 62(9):2606–2610PubMed
13.
Hu J, You S, Li W, Wang D, Nagpal ML, Mi Y, Liang P, Lin T (1998) Expression and regulation of interferon-gamma-inducible protein 10 gene in rat Leydig cells. Endocrinology 139(8):3637–3645PubMed
14.
Chu Y, Yang X, Xu W, Wang Y, Guo Q, Xiong S (2007) In situ expression of IFN-gamma-inducible T cell alpha chemoattractant in breast cancer mounts an enhanced specific anti-tumor immunity which leads to tumor regression. Cancer Immunol Immunother 56(10):1539–1549. doi:10.​1007/​s00262-007-0296-1 CrossRefPubMed
15.
Datta D, Flaxenburg JA, Laxmanan S, Geehan C, Grimm M, Waaga-Gasser AM, Briscoe DM, Pal S (2006) Ras-induced modulation of CXCL10 and its receptor splice variant CXCR3-B in MDA-MB-435 and MCF-7 cells: relevance for the development of human breast cancer. Cancer Res 66(19):9509–9518CrossRefPubMed
16.
Ma X, Norsworthy K, Kundu N, Rodgers WH, Gimotty PA, Goloubeva O, Lipsky M, Li Y, Holt D, Fulton A (2009) CXCR3 expression is associated with poor survival in breast cancer and promotes metastasis in a murine model. Mol Cancer Ther 8(3):490–498CrossRefPubMed
17.
Lasagni L, Francalanci M, Annunziato F, Lazzeri E, Giannini S, Cosmi L, Sagrinati C, Mazzinghi B, Orlando C, Maggi E, Marra F, Romagnani S, Serio M, Romagnani P (2003) An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4. J Exp Med 197(11):1537–1549PubMedCentralCrossRefPubMed
18.
19.
Aronica SM, Fanti P, Kaminskaya K, Gibbs K, Raiber L, Nazareth M, Bucelli R, Mineo M, Grzybek K, Kumin M, Poppenberg K, Schwach C, Janis K (2004) Estrogen disrupts chemokine-mediated chemokine release from mammary cells: implications for the interplay between estrogen and IP-10 in the regulation of mammary tumor formation. Breast Cancer Res Treat 84(3):235–245. doi:10.​1023/​B:​BREA.​0000019961.​59306.​f6 CrossRefPubMed
20.
21.
22.
McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM, Statistics Subcommittee of NCIEWGoCD (2006) Reporting recommendations for tumor marker prognostic studies (REMARK). Breast Cancer Res Treat 100(2):229–235. doi:10.​1007/​s10549-006-9242-8 CrossRefPubMed
23.
Rutqvist LE, Johansson H, Stockholm Breast Cancer Study Group (2007) Long-term follow-up of the randomized Stockholm trial on adjuvant tamoxifen among postmenopausal patients with early stage breast cancer. Acta Oncol 46(2):133–145CrossRefPubMed
24.
Jansson A, Delander L, Gunnarsson C, Fornander T, Skoog L, Nordenskjold B, Stal O (2009) Ratio of 17HSD1 to 17HSD2 protein expression predicts the outcome of tamoxifen treatment in postmenopausal breast cancer patients. Clin Cancer Res 15(10):3610–3616CrossRefPubMed
25.
Aronica SM, Raiber L, Hanzly M, Kisela C (2009) Antitumor/antiestrogenic effect of the chemokine interferon inducible protein 10 (IP-10) involves suppression of VEGF expression in mammary tissue. J Interferon Cytokine Res 29(2):83–92. doi:10.​1089/​jir.​2008.​0034 CrossRefPubMed
26.
Aksoy MO, Yang Y, Ji R, Reddy PJ, Shahabuddin S, Litvin J, Rogers TJ, Kelsen SG (2006) CXCR3 surface expression in human airway epithelial cells: cell cycle dependence and effect on cell proliferation. Am J Physiol Lung Cell Mol Physiol 290(5):L909–L918CrossRefPubMed
27.
Romagnani P, Annunziato F, Lasagni L, Lazzeri E, Beltrame C, Francalanci M, Uguccioni M, Galli G, Cosmi L, Maurenzig L, Baggiolini M, Maggi E, Romagnani S, Serio M (2001) Cell cycle-dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity. J Clin Investig 107(1):53–63PubMedCentralCrossRefPubMed
28.
Janis K, Hoeltke J, Nazareth M, Fanti P, Poppenberg K, Aronica SM (2004) Estrogen decreases expression of chemokine receptors, and suppresses chemokine bioactivity in murine monocytes. Am J Reprod Immunol 51(1):22–31CrossRefPubMed
29.
Kawada K, Sonoshita M, Sakashita H, Takabayashi A, Yamaoka Y, Manabe T, Inaba K, Minato N, Oshima M, Taketo MM (2004) Pivotal role of CXCR3 in melanoma cell metastasis to lymph nodes. Cancer Res 64(11):4010–4017CrossRefPubMed
30.
Cambien B, Karimdjee BF, Richard-Fiardo P, Bziouech H, Barthel R, Millet MA, Martini V, Birnbaum D, Scoazec JY, Abello J, Al Saati T, Johnson MG, Sullivan TJ, Medina JC, Collins TL, Schmid-Alliana A, Schmid-Antomarchi H (2009) Organ-specific inhibition of metastatic colon carcinoma by CXCR3 antagonism. Br J Cancer 100(11):1755–1764. doi:10.​1038/​sj.​bjc.​6605078 PubMedCentralCrossRefPubMed
31.
Kawada K, Hosogi H, Sonoshita M, Sakashita H, Manabe T, Shimahara Y, Sakai Y, Takabayashi A, Oshima M, Taketo MM (2007) Chemokine receptor CXCR3 promotes colon cancer metastasis to lymph nodes. Oncogene 26(32):4679–4688. doi:10.​1038/​sj.​onc.​1210267 CrossRefPubMed
32.
33.
34.
35.
Datta D, Banerjee P, Gasser M, Waaga-Gasser AM, Pal S (2010) CXCR3-B can mediate growth-inhibitory signals in human renal cancer cells by down-regulating the expression of heme oxygenase-1. J Biol Chem 285(47):36842–36848PubMedCentralCrossRefPubMed
Metadata
Title
C–X–C ligand 10 and C–X–C receptor 3 status can predict tamoxifen treatment response in breast cancer patients
Authors
Erik Hilborn
Tove Sivik
Tommy Fornander
Olle Stål
Bo Nordenskjöld
Agneta Jansson
Publication date
01-05-2014
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2014
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-014-2933-7

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