Assessment of CXC ligand 12-mediated calcium signalling and its regulators in basal-like breast cancer cells

Jamaludin,S. Y. N.; Azimi,I.; Davis,F. M.; Peters,A. A.; Gonda,T. J.; Thompson,E. W.; Roberts‑Thomson,S. J.; Monteith,G. R.

doi:10.3892/ol.2018.7827

Assessment of CXC ligand 12-mediated calcium signalling and its regulators in basal-like breast cancer cells

Authors:
- S. Y. N. Jamaludin
- I. Azimi
- F. M. Davis
- A. A. Peters
- T. J. Gonda
- E. W. Thompson
- S. J. Roberts‑Thomson
- G. R. Monteith
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Affiliations: School of Pharmacy, Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, Queensland 4102, Australia, The Translational Research Institute, Brisbane, Queensland 4102, Australia
Published online on: January 19, 2018 https://doi.org/10.3892/ol.2018.7827
Pages: 4289-4295
Copyright: © Jamaludin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

CXC ligand (L)12 is a chemokine implicated in the migration, invasion and metastasis of cancer cells via interaction with its receptors CXC chemokine receptor (CXCR)4 and CXCR7. In the present study, CXCL12‑mediated Ca2+ signalling was compared with two basal‑like breast cancer cell lines, MDA‑MB‑231 and MDA‑MB‑468, which demonstrate distinct metastatic potential. CXCL12 treatment induced Ca2+ responses in the more metastatic MDA‑MB‑231 cells but not in the less metastatic MDA‑MB‑468 cells. Assessment of mRNA levels of CXCL12 receptors and their potential modulators in both cell lines revealed that CXCR4 and CXCR7 levels were increased in MDA‑MB‑231 cells compared with MDA‑MB‑468 cells. Cluster of differentiation (CD)24, the negative regulator of CXCL12 responses, demonstrated increased expression in MDA‑MB‑468 cells compared with MDA‑MB‑231 cells, and the two cell lines expressed comparable levels of hypoxia‑inducible factor (HIF)2α, a CXCR4 regulator. Induction of epithelial-mesenchymal transition (EMT) by epidermal growth factor exhibited opposite effects on CXCR4 mRNA levels compared with hypoxia‑induced EMT. Neither EMT inducer exhibited an effect on CXCR7 expression, however hypoxia increased HIF2α expression levels in MDA‑MB‑468 cells. Analysis of the gene expression profiles of breast tumours revealed that the highest expression levels of CXCR4 and CXCR7 were in the Claudin‑Low molecular subtype, which is markedly associated with EMT features.

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1	Rossi D and Zlotnik A: The biology of chemokines and their receptors. Annu Rev Immunol. 18:217–242. 2000. View Article : Google Scholar : PubMed/NCBI
2	Perissinotto E, Cavalloni G, Leone F, Fonsato V, Mitola S, Grignani G, Surrenti N, Sangiolo D, Bussolino F, Piacibello W and Aglietta M: Involvement of chemokine receptor 4/stromal cell-derived factor 1 system during osteosarcoma tumor progression. Clin Cancer Res. 11:490–497. 2005.PubMed/NCBI
3	Geminder H, Sagi-Assif O, Goldberg L, Meshel T, Rechavi G, Witz IP and Ben-Baruch A: A possible role for CXCR4 and its ligand, the CXC chemokine stromal cell-derived factor-1, in the development of bone marrow metastases in neuroblastoma. J Immunol. 167:4747–4757. 2001. View Article : Google Scholar : PubMed/NCBI
4	Mochizuki H, Matsubara A, Teishima J, Mutaguchi K, Yasumoto H, Dahiya R, Usui T and Kamiya K: Interaction of ligand-receptor system between stromal-cell-derived factor-1 and CXC chemokine receptor 4 in human prostate cancer: A possible predictor of metastasis. Biochem Biophys Res Commun. 320:656–663. 2004. View Article : Google Scholar : PubMed/NCBI
5	Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, et al: Involvement of chemokine receptors in breast cancer metastasis. Nature. 410:50–56. 2001. View Article : Google Scholar : PubMed/NCBI
6	Balabanian K, Lagane B, Infantino S, Chow KY, Harriague J, Moepps B, Arenzana-Seisdedos F, Thelen M and Bachelerie F: The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes. J Biol Chem. 280:35760–35766. 2005. View Article : Google Scholar : PubMed/NCBI
7	Teicher BA and Fricker SP: CXCL12 (SDF-1)/CXCR4 pathway in cancer. Clin Cancer Res. 16:2927–2931. 2010. View Article : Google Scholar : PubMed/NCBI
8	Sun X, Cheng G, Hao M, Zheng J, Zhou X, Zhang J, Taichman RS, Pienta KJ and Wang J: CXCL12/CXCR4/CXCR7 chemokine axis and cancer progression. Cancer Metastasis Rev. 29:709–722. 2010. View Article : Google Scholar : PubMed/NCBI
9	Kang H, Watkins G, Parr C, Douglas-Jones A, Mansel RE and Jiang WG: Stromal cell derived factor-1: Its influence on invasiveness and migration of breast cancer cells in vitro, and its association with prognosis and survival in human breast cancer. Breast Cancer Res. 7:R402–R410. 2005. View Article : Google Scholar : PubMed/NCBI
10	Mukherjee D and Zhao J: The role of chemokine receptor CXCR4 in breast cancer metastasis. Am J Cancer Res. 3:46–57. 2013.PubMed/NCBI
11	Xu C, Zhao H, Chen H and Yao Q: CXCR4 in breast cancer: Oncogenic role and therapeutic targeting. Drug Des Dev Ther. 9:4953–4964. 2015.
12	Kay R, Rosten PM and Humphries RK: CD24, a signal transducer modulating B cell activation responses, is a very short peptide with a glycosyl phosphatidylinositol membrane anchor. J Immunol. 147:1412–1416. 1991.PubMed/NCBI
13	Schabath H, Runz S, Joumaa S and Altevogt P: CD24 affects CXCR4 function in pre-B lymphocytes and breast carcinoma cells. J Cell Sci. 119:314–325. 2006. View Article : Google Scholar : PubMed/NCBI
14	Imtiyaz HZ, Williams EP, Hickey MM, Patel SA, Durham AC, Yuan LJ, Hammond R, Gimotty PA, Keith B and Simon MC: Hypoxia-inducible factor 2alpha regulates macrophage function in mouse models of acute and tumor inflammation. J Clin Invest. 120:2699–2714. 2010. View Article : Google Scholar : PubMed/NCBI
15	Prevarskaya N, Skryma R and Shuba Y: Calcium in tumour metastasis: New roles for known actors. Nat Rev Cancer. 11:609–618. 2011. View Article : Google Scholar : PubMed/NCBI
16	Azimi I, Roberts-Thomson SJ and Monteith GR: Calcium influx pathways in breast cancer: Opportunities for pharmacological intervention. Br J Pharmacol. 171:945–960. 2014. View Article : Google Scholar : PubMed/NCBI
17	Davis FM, Kenny PA, Soo ET, van Denderen BJ, Thompson EW, Cabot PJ, Parat MO, Roberts-Thomson SJ and Monteith GR: Remodeling of purinergic receptor-mediated Ca2+ signaling as a consequence of EGF-induced epithelial-mesenchymal transition in breast cancer cells. PLoS One. 6:e234642011. View Article : Google Scholar : PubMed/NCBI
18	Azimi I and Monteith GR: Plasma membrane ion channels and epithelial to mesenchymal transition in cancer cells. Endocr Relat Cancer. 23:R517–R525. 2016. View Article : Google Scholar : PubMed/NCBI
19	McAndrew D, Grice DM, Peters AA, Davis FM, Stewart T, Rice M, Smart CE, Brown MA, Kenny PA, Roberts-Thomson SJ and Monteith GR: ORAI1-mediated calcium influx in lactation and in breast cancer. Mol Cancer Ther. 10:448–460. 2011. View Article : Google Scholar : PubMed/NCBI
20	Motiani RK, Abdullaev IF and Trebak M: A novel native store-operated calcium channel encoded by Orai3: Selective requirement of Orai3 versus Orai1 in estrogen receptor-positive versus estrogen receptor-negative breast cancer cells. J Biol Chem. 285:19173–19183. 2010. View Article : Google Scholar : PubMed/NCBI
21	Peters AA, Simpson PT, Bassett JJ, Lee JM, Da Silva L, Reid LE, Song S, Parat MO, Lakhani SR, Kenny PA, et al: Calcium channel TRPV6 as a potential therapeutic target in estrogen receptor-negative breast cancer. Mol Cancer Ther. 11:2158–2168. 2012. View Article : Google Scholar : PubMed/NCBI
22	Badve S, Dabbs DJ, Schnitt SJ, Baehner FL, Decker T, Eusebi V, Fox SB, Ichihara S, Jacquemier J, Lakhani SR, et al: Basal-like and triple-negative breast cancers: A critical review with an emphasis on the implications for pathologists and oncologists. Mod Pathol. 24:157–167. 2011. View Article : Google Scholar : PubMed/NCBI
23	Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, Fevr T, Clark L, Bayani N, Coppe JP, Tong F, et al: A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell. 10:515–527. 2006. View Article : Google Scholar : PubMed/NCBI
24	Aung CS, Ye W, Plowman G, Peters AA, Monteith GR and Roberts-Thomson SJ: Plasma membrane calcium ATPase 4 and the remodeling of calcium homeostasis in human colon cancer cells. Carcinogenesis. 30:1962–1969. 2009. View Article : Google Scholar : PubMed/NCBI
25	Stewart TA, Azimi I, Brooks AJ, Thompson EW, Roberts-Thomson SJ and Monteith GR: Janus kinases and Src family kinases in the regulation of EGF-induced vimentin expression in MDA-MB-468 breast cancer cells. Int J Biochem Cell Biol. 76:64–74. 2016. View Article : Google Scholar : PubMed/NCBI
26	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
27	Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, et al: The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2:401–404. 2012. View Article : Google Scholar : PubMed/NCBI
28	Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, Sun Y, Jacobsen A, Sinha R, Larsson E, et al: Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 6:pl12013. View Article : Google Scholar : PubMed/NCBI
29	Pereira B, Chin SF, Rueda OM, Vollan HK, Provenzano E, Bardwell HA, Pugh M, Jones L, Russell R, Sammut SJ, et al: Erratum: The somatic mutation profiles of 2,433 breast cancers refine their genomic and transcriptomic. Nat Commun. 7:119082016. View Article : Google Scholar : PubMed/NCBI
30	Charafe-Jauffret E, Ginestier C, Monville F, Finetti P, Adélaïde J, Cervera N, Fekairi S, Xerri L, Jacquemier J, Birnbaum D and Bertucci F: Gene expression profiling of breast cell lines identifies potential new basal markers. Oncogene. 25:2273–2284. 2006. View Article : Google Scholar : PubMed/NCBI
31	Davis FM, Azimi I, Faville RA, Peters AA, Jalink K, Putney JW Jr, Goodhill GJ, Thompson EW, Roberts-Thomson SJm and Monteith GR: Induction of epithelial-mesenchymal transition (EMT) in breast cancer cells is calcium signal dependent. Oncogene. 33:2307–2316. 2014. View Article : Google Scholar : PubMed/NCBI
32	Azimi I, Beilby H, Davis FM, Marcial DL, Kenny PA, Thompson EW, Roberts-Thomson SJ and Monteith GR: Altered purinergic receptor-Ca² signaling associated with hypoxia-induced epithelial-mesenchymal transition in breast cancer cells. Mol Oncol. 10:166–178. 2016. View Article : Google Scholar : PubMed/NCBI
33	Azimi I, Milevskiy MJG, Kaemmerer E, Turner D, Yapa KTDS, Brown MA, Thompson EW, Roberts-Thomson SJ and Monteith GR: TRPC1 is a differential regulator of hypoxia-mediated events and Akt signalling in PTEN-deficient breast cancer cells. J Cell Sci. 130:2292–2305. 2017. View Article : Google Scholar : PubMed/NCBI
34	Hennessy BT, Gonzalez-Angulo AM, Stemke-Hale K, Gilcrease MZ, Krishnamurthy S, Lee JS, Fridlyand J, Sahin A, Agarwal R, Joy C, et al: Characterization of a naturally occurring breast cancer subset enriched in epithelial-to-mesenchymal transition and stem cell characteristics. Cancer Res. 69:4116–4124. 2009. View Article : Google Scholar : PubMed/NCBI
35	Holland JD, Kochetkova M, Akekawatchai C, Dottore M, Lopez A and McColl SR: Differential functional activation of chemokine receptor CXCR4 is mediated by G proteins in breast cancer cells. Cancer Res. 66:4117–4124. 2006. View Article : Google Scholar : PubMed/NCBI
36	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
37	Salvucci O, Bouchard A, Baccarelli A, Deschênes J, Sauter G, Simon R, Bianchi R and Basik M: The role of CXCR4 receptor expression in breast cancer: A large tissue microarray study. Breast Cancer Res Treat. 97:275–283. 2006. View Article : Google Scholar : PubMed/NCBI
38	Blick T, Hugo H, Widodo E, Pinto C, Mani SA, Weinberg RA, Neve RM, Lenburg ME and Thompson EW: Epithelial mesenchymal transition traits in human breast cancer cell lines parallel the CD44(hi/)CD24(lo/-) stem cell phenotype in human breast cancer. J Mammary Gland Biol Neoplasia. 15:235–252. 2010. View Article : Google Scholar : PubMed/NCBI
39	Schindelmann S, Windisch J, Grundmann R, Kreienberg R, Zeillinger R and Deissler H: Expression profiling of mammary carcinoma cell lines: Correlation of in vitro invasiveness with expression of CD24. Tumor Biol. 23:139–145. 2002. View Article : Google Scholar
40	Blick T, Widodo E, Hugo H, Waltham M, Lenburg ME, Neve RM and Thompson EW: Epithelial mesenchymal transition traits in human breast cancer cell lines. Clin Exp Metastasis. 25:629–642. 2008. View Article : Google Scholar : PubMed/NCBI
41	Bertran E, Caja L, Navarro E, Sancho P, Mainez J, Murillo MM, Vinyals A, Fabra A and Fabregat I: Role of CXCR4/SDF-1 alpha in the migratory phenotype of hepatoma cells that have undergone epithelial-mesenchymal transition in response to the transforming growth factor-beta. Cell Signal. 21:1595–1606. 2009. View Article : Google Scholar : PubMed/NCBI
42	Prat A, Parker JS, Karginova O, Fan C, Livasy C, Herschkowitz JI, He X and Perou CM: Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res. 12:R682010. View Article : Google Scholar : PubMed/NCBI