Benzyl butyl phthalate increases the chemoresistance to doxorubicin/cyclophosphamide by increasing breast cancer-associated dendritic cell-derived CXCL1/GROα and S100A8/A9

Hsu,Ya-Ling; Hung,Jen-Yu; Tsai,Eing-Mei; Wu,Cheng-Ying; Ho,Ya-Wen; Jian,Shu-Fang; Yen,Meng-Chi; Chang,Wei-An; Hou,Ming-Feng; Kuo,Po-Lin

doi:10.3892/or.2015.4307

Benzyl butyl phthalate increases the chemoresistance to doxorubicin/cyclophosphamide by increasing breast cancer-associated dendritic cell-derived CXCL1/GROα and S100A8/A9

Authors:
- Ya-Ling Hsu
- Jen-Yu Hung
- Eing-Mei Tsai
- Cheng-Ying Wu
- Ya-Wen Ho
- Shu-Fang Jian
- Meng-Chi Yen
- Wei-An Chang
- Ming-Feng Hou
- Po-Lin Kuo
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Affiliations: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C., School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C., Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C., Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C., Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan, R.O.C.
Published online on: September 23, 2015 https://doi.org/10.3892/or.2015.4307
Pages: 2889-2900

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Abstract

Phthalates are used as plasticizers in the manufacture of flexible vinyl, which is used in food contact applications. Phthalates have been demonstrated to have an adverse impact on human health, particularly in terms of cancer development. In the present study, we showed for the first time that benzyl butyl phthalate (BBP) potentiates the effect of tumor‑associated dendritic cells (TADCs) on the chemoresistance of breast cancer. Specific knockdown analysis revealed that S100A9 is the major factor responsible for the chemoresistance of doxorubicin/cyclophosphamide induced by BBP-stimulated TADCs in breast cancer. BBP exposure also increased tumor infiltrating myeloid-derived suppressor cell (MDSC) secretion of S100A8/A9, thereby exacerbating the resistance of breast cancer to doxorubicin with cyclophosphamide. In addition, BBP also stimulated the production of CXCL1/GROα by TADCs, which increased the angiogenesis of breast cancer in a mouse model. Inhibition of CXCL1/GROα by a neutralizing antibody, decreased the BBP-induced angiogenesis induced by BBP after chemotherapy in the mouse model. These results, for the first time, provide evidence that BBP influences the efficacy of chemotherapy by remodeling the tumor microenvironment of breast cancer.

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1	Cirillo T, Fasano E, Castaldi E, Montuori P and Amodio Cocchieri R: Children's exposure to Di(2-ethylhexyl) phthalate and dibutylphthalate plasticizers from school meals. J Agric Food Chem. 59:10532–10538. 2011. View Article : Google Scholar : PubMed/NCBI
2	Casajuana N and Lacorte S: New methodology for the determination of phthalate esters, bisphenol A, bisphenol A diglycidyl ether, and nonylphenol in commercial whole milk samples. J Agric Food Chem. 52:3702–3707. 2004. View Article : Google Scholar : PubMed/NCBI
3	Wu Z, Zhang X, Wu X, Shen G, Du Q and Mo C: Uptake of di(2-ethylhexyl) phthalate (DEHP) by the plant Benincasa hispida and its use for lowering DEHP content of intercropped vegetables. J Agric Food Chem. 61:5220–5225. 2013. View Article : Google Scholar : PubMed/NCBI
4	Liu Y, Wang S and Wang L: Development of rapid determination of 18 phthalate esters in edible vegetable oils by gas chromatography tandem mass spectrometry. J Agric Food Chem. 61:1160–1164. 2013. View Article : Google Scholar : PubMed/NCBI
5	Yan H, Cheng X and Yang G: Dummy molecularly imprinted solid-phase extraction for selective determination of five phthalate esters in plastic bottled functional beverages. J Agric Food Chem. 60:5524–5531. 2012. View Article : Google Scholar : PubMed/NCBI
6	Sun H, Yang Y, Li H, Zhang J and Sun N: Development of multi-residue analysis for twenty phthalate esters in edible vegetable oils by microwave-assisted extraction-gel permeation chromatography-solid phase extraction-gas chromatography-tandem mass spectrometry. J Agric Food Chem. 60:5532–5539. 2012. View Article : Google Scholar : PubMed/NCBI
7	Fu X and Du Q: Uptake of di-(2-ethylhexyl) phthalate of vegetables from plastic film greenhouses. J Agric Food Chem. 59:11585–11588. 2011. View Article : Google Scholar : PubMed/NCBI
8	Guo Y, Zhang Z, Liu L, Li Y, Ren N and Kannan K: Occurrence and profiles of phthalates in foodstuffs from China and their implications for human exposure. J Agric Food Chem. 60:6913–6919. 2012. View Article : Google Scholar : PubMed/NCBI
9	Cirillo T, Latini G, Castaldi MA, Dipaola L, Fasano E, Esposito F, Scognamiglio G, Francesco FD and Cobellis L: Exposure to di-2-ethylhexyl phthalate, di-n-butyl phthalate and bisphenol A through infant formulas. J Agric Food Chem. 63:3303–3310. 2015. View Article : Google Scholar : PubMed/NCBI
10	Gaspar FW, Castorina R, Maddalena RL, Nishioka MG, McKone TE and Bradman A: Phthalate exposure and risk assessment in California child care facilities. Environ Sci Technol. 48:7593–7601. 2014. View Article : Google Scholar : PubMed/NCBI
11	Hsieh TH, Tsai CF, Hsu CY, Kuo PL, Lee Jn, Chai CY, Wang SC and Tsai EM: Phthalates induce proliferation and invasiveness of estrogen receptor-negative breast cancer through the AhR/HDAC6/c-Myc signaling pathway. FASEB J. 26:778–787. 2012. View Article : Google Scholar
12	Carran M and Shaw IC: New Zealand Malayan war veterans' exposure to dibutylphthalate is associated with an increased incidence of cryptorchidism, hypospadias and breast cancer in their children. NZ Med J. 125:52–63. 2012.
13	Fernandez SV and Russo J: Estrogen and xenoestrogens in breast cancer. Toxicol Pathol. 38:110–122. 2010. View Article : Google Scholar :
14	Chen FP and Chien MH: Lower concentrations of phthalates induce proliferation in human breast cancer cells. Climacteric. 17:377–384. 2014. View Article : Google Scholar
15	Hsieh TH, Tsai CF, Hsu CY, Kuo PL, Hsi E, Suen JL, Hung CH, Lee JN, Chai CY, Wang SC, et al: n-Butyl benzyl phthalate promotes breast cancer progression by inducing expression of lymphoid enhancer factor 1. PLoS One. 7:e427502012. View Article : Google Scholar : PubMed/NCBI
16	Hsieh TH, Tsai CF, Hsu CY, Kuo PL, Lee JN, Chai CY, Hou MF, Chang CC, Long CY, Ko YC, et al: Phthalates stimulate the epithelial to mesenchymal transition through an HDAC6-dependent mechanism in human breast epithelial stem cells. Toxicol Sci. 128:365–376. 2012. View Article : Google Scholar : PubMed/NCBI
17	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
18	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar
19	Roché H and Vahdat LT: Treatment of metastatic breast cancer: Second line and beyond. Ann Oncol. 22:1000–1010. 2011. View Article : Google Scholar
20	Hu G, Chong RA, Yang Q, Wei Y, Blanco MA, Li F, Reiss M, Au JL, Haffty BG and Kang Y: MTDH activation by 8q22 genomic gain promotes chemoresistance and metastasis of poor-prognosis breast cancer. Cancer Cell. 15:9–20. 2009. View Article : Google Scholar :
21	Klemm F and Joyce JA: Microenvironmental regulation of therapeutic response in cancer. Trends Cell Biol. 25:198–213. 2015. View Article : Google Scholar
22	Grivennikov SI, Greten FR and Karin M: Immunity, inflammation, and cancer. Cell. 140:883–899. 2010. View Article : Google Scholar : PubMed/NCBI
23	Weizman N, Krelin Y, Shabtay-Orbach A, Amit M, Binenbaum Y, Wong RJ and Gil Z: Macrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by upregulating cytidine deaminase. Oncogene. 33:3812–3819. 2014. View Article : Google Scholar
24	Mitchem JB, Brennan DJ, Knolhoff BL, Belt BA, Zhu Y, Sanford DE, Belaygorod L, Carpenter D, Collins L, Piwnica-Worms D, et al: Targeting tumor-infiltrating macro phages decreases tumor-initiating cells, relieves immunosuppression, and improves chemotherapeutic responses. Cancer Res. 73:1128–1141. 2013. View Article : Google Scholar :
25	Hsu YL, Hung JY, Tsai YM, Tsai EM, Huang MS, Hou MF and Kuo PL: 6-shogaol, an active constituent of dietary ginger, impairs cancer development and lung metastasis by inhibiting the secretion of CC-chemokine ligand 2 (CCL2) in tumor-associated dendritic cells. J Agric Food Chem. 63:1730–1738. 2015. View Article : Google Scholar : PubMed/NCBI
26	Kan JY, Wu DC, Yu FJ, Wu CY, Ho YW, Chiu YJ, Jian SF, Hung JY, Wang JY and Kuo PL: Chemokine (C-C motif) ligand 5 is involved in tumor-associated dendritic cell-mediated colon cancer progression through non-coding RNA MALAT-1. J Cell Physiol. 230:1883–1894. 2015. View Article : Google Scholar
27	Kuo PL, Huang MS, Cheng DE, Hung JY, Yang CJ and Chou SH: Lung cancer-derived galectin-1 enhances tumorigenic potentiation of tumor-associated dendritic cells by expressing heparin-binding EGF-like growth factor. J Biol Chem. 287:9753–9764. 2012. View Article : Google Scholar : PubMed/NCBI
28	Tang XH, Deng S, Li M and Lu MS: The anti-tumor effect of cross-reacting material 197, an inhibitor of heparin-binding EGF-like growth factor, in human resistant ovarian cancer. Biochem Biophys Res Commun. 422:676–680. 2012. View Article : Google Scholar : PubMed/NCBI
29	Qian DZ, Rademacher BL, Pittsenbarger J, Huang CY, Myrthue A, Higano CS, Garzotto M, Nelson PS and Beer TM: CCL2 is induced by chemotherapy and protects prostate cancer cells from docetaxel-induced cytotoxicity. Prostate. 70:433–442. 2010.
30	Lee E, Lee SJ, Koskimaki JE, Han Z, Pandey NB and Popel AS: Inhibition of breast cancer growth and metastasis by a biomimetic peptide. Sci Rep. 4:71392014. View Article : Google Scholar : PubMed/NCBI
31	Acharyya S, Oskarsson T, Vanharanta S, Malladi S, Kim J, Morris PG, Manova-Todorova K, Leversha M, Hogg N, Seshan VE, et al: A CXCL1 paracrine network links cancer chemoresistance and metastasis. Cell. 150:165–178. 2012. View Article : Google Scholar : PubMed/NCBI
32	Wang L, Chang EWY, Wong SC, Ong SM, Chong DQY and Ling KL: Increased myeloid-derived suppressor cells in gastric cancer correlate with cancer stage and plasma S100A8/A9 proinflammatory proteins. J Immunol. 190:794–804. 2013. View Article : Google Scholar
33	Miyake M, Goodison S, Urquidi V, Gomes Giacoia E and Rosser CJ: Expression of CXCL1 in human endothelial cells induces angiogenesis through the CXCR2 receptor and the ERK1/2 and EGF pathways. Lab Invest. 93:768–778. 2013. View Article : Google Scholar : PubMed/NCBI
34	Palucka K, Coussens LM and O'Shaughnessy J: Dendritic cells, inflammation, and breast cancer. Cancer J. 19:511–516. 2013. View Article : Google Scholar : PubMed/NCBI
35	Coussens LM, Zitvogel L and Palucka AK: Neutralizing tumor-promoting chronic inflammation: A magic bullet? Science. 339:286–291. 2013. View Article : Google Scholar : PubMed/NCBI
36	Hartmann TN, Burger JA, Glodek A, Fujii N and Burger M: CXCR4 chemokine receptor and integrin signaling co-operate in mediating adhesion and chemoresistance in small cell lung cancer (SCLC) cells. Oncogene. 24:4462–4471. 2005. View Article : Google Scholar : PubMed/NCBI
37	Angst E, Reber HA, Hines OJ and Eibl G: Mononuclear cell-derived interleukin-1 beta confers chemoresistance in pancreatic cancer cells by upregulation of cyclooxygenase-2. Surgery. 144:57–65. 2008. View Article : Google Scholar : PubMed/NCBI
38	Chen R, Alvero AB, Silasi DA and Mor G: Inflammation, cancer and chemoresistance: Taking advantage of the toll-like receptor signaling pathway. Am J Reprod Immunol. 57:93–107. 2007. View Article : Google Scholar : PubMed/NCBI
39	Srikrishna G: S100A8 and S100A9: New insights into their roles in malignancy. J Innate Immun. 4:31–40. 2012. View Article : Google Scholar :
40	Ichikawa M, Williams R, Wang L, Vogl T and Srikrishna G: S100A8/A9 activate key genes and pathways in colon tumor progression. Mol Cancer Res. 9:133–148. 2011. View Article : Google Scholar : PubMed/NCBI
41	Yang M, Zeng P, Kang R, Yu Y, Yang L, Tang D and Cao L: S100A8 contributes to drug resistance by promoting autophagy in leukemia cells. PLoS One. 9:e972422014. View Article : Google Scholar : PubMed/NCBI
42	Zou A, Lambert D, Yeh H, Yasukawa K, Behbod F, Fan F and Cheng N: Elevated CXCL1 expression in breast cancer stroma predicts poor prognosis and is inversely associated with expression of TGF-β signaling proteins. BMC Cancer. 14:7812014. View Article : Google Scholar
43	Pecot CV, Rupaimoole R, Yang D, Akbani R, Ivan C, Lu C, Wu S, Han HD, Shah MY, Rodriguez-Aguayo C, et al: Tumour angiogenesis regulation by the miR-200 family. Nat Commun. 4:24272013. View Article : Google Scholar : PubMed/NCBI
44	Nishioka J, Iwahara C, Kawasaki M, Yoshizaki F, Nakayama H, Takamori K, Ogawa H and Iwabuchi K: Di-(2-ethylhexyl) phthalate induces production of inflammatory molecules in human macrophages. Inflamm Res. 61:69–78. 2012. View Article : Google Scholar