Acidic microenvironment induction of interleukin-8 expression and matrix metalloproteinase-2/-9 activation via acid-sensing ion channel 1 promotes breast cancer cell progression

Nakanishi,Masako; Korechika,Ayaka; Yamakawa,Haruka; Kawabe,Naoko; Nakai,Kazuma; Muragaki,Yasuteru

doi:10.3892/or.2020.7907

Acidic microenvironment induction of interleukin-8 expression and matrix metalloproteinase-2/-9 activation via acid-sensing ion channel 1 promotes breast cancer cell progression

Authors:
- Masako Nakanishi
- Ayaka Korechika
- Haruka Yamakawa
- Naoko Kawabe
- Kazuma Nakai
- Yasuteru Muragaki
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Affiliations: Department of Pathology, Wakayama Medical University, Wakayama 641-8509, Japan
Published online on: December 24, 2020 https://doi.org/10.3892/or.2020.7907
Pages: 1284-1294

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Abstract

The cancer microenvironment exhibits local acidosis compared with the surrounding normal tissue. Many reports have shown that acidosis accelerates the invasiveness and metastasis of cancer, yet the underlying molecular mechanisms remain unclear. In the present study, we focused on acid-induced functional changes through acid receptors in breast cancer cells. Acidic treatment induced interleukin (IL)-8 expression in MDA-MB-231 cells and promoted cell migration and invasion. The acidic microenvironment elevated matrix metalloproteinase (MMP)-2 and MMP-9 activity, and addition of IL-8 had similar effects. However, inhibition of IL-8 suppressed the acid-induced migration and invasion of MDA-MB-231 cells. MDA-MB-231 cells express various acid receptors including ion channels and G protein-coupled receptors. Interestingly, acidic stimulation increased the expression of acid-sensing ion channel 1 (ASIC1), and acid-induced IL-8 was significantly decreased by ASIC1 knockdown. Moreover, phosphorylation of nuclear factor (NF)-κB was induced by acidic treatment, and inhibition of NF-κB activation reduced acid-induced IL-8 expression. These results suggest that IL-8 induction by an acidic microenvironment promotes breast cancer development and that ASIC1 might be a novel therapeutic target for breast cancer metastasis.

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1	Justus CR, Dong L and Yang LV: Acidic tumor microenvironment and pH-sensing G protein-coupled receptors. Front Physiol. 4:3542013. View Article : Google Scholar : PubMed/NCBI
2	Estrella V, Chen T, Lloyd M, Wojtkowiak J, Cornnell HH, Ibrahim-Hashim A, Bailey K, Balagurunathan Y, Rothberg JM, Sloane BF, et al: Acidity generated by the tumor microenvironment drives local invasion. Cancer Res. 73:1524–1535. 2013. View Article : Google Scholar : PubMed/NCBI
3	Damaghi M, Wojtkowiak JW and Gillies RJ: pH sensing and regulation in cancer. Front Physiol. 4:3702013. View Article : Google Scholar : PubMed/NCBI
4	Kato Y, Ozawa S, Miyamoto C, Maehata Y, Suzuki A, Maeda T and Baba Y: Acidic extracellular microenvironment and cancer. Cancer Cell Int. 13:89–96. 2013. View Article : Google Scholar : PubMed/NCBI
5	Boedtkjer E and Pedersen SF: The acidic tumor microenvironment as a driver of cancer. Annu Rev Physiol. 82:103–126. 2020. View Article : Google Scholar : PubMed/NCBI
6	Rofstad EK, Mathiesen B, Kindem K and Galappathi K: Acidic extracellular pH promotes experimental metastasis of human melanoma cells in athymic nude mice. Cancer Res. 66:6699–6707. 2006. View Article : Google Scholar : PubMed/NCBI
7	Nishisho T, Hata K, Nakanishi M, Morita Y, Sun-Wada GH, Wada Y, Yasui N and Yoneda T: The a3 isoform vacuolar type H(+)-ATPase promotes distant metastasis in the mouse B16 melanoma cells. Mol Cancer Res. 9:845–855. 2011. View Article : Google Scholar : PubMed/NCBI
8	Waugh DJ and Wilson C: The interleukin-8 pathway in cancer. Clin Cancer Res. 14:6735–6741. 2008. View Article : Google Scholar : PubMed/NCBI
9	Zarogoulidis P, Katsikogianni F, Tsiouda T, Sakkas A, Katsikogiannis N and Zarogoulidis K: Interleukin-8 and interleukin-17 for cancer. Cancer Invest. 32:197–205. 2014. View Article : Google Scholar : PubMed/NCBI
10	Srivastava SK, Bhardwaj A, Arora S, Tyagi N, Singh AP, Carter JE, Scammell JG, Fodstad Ø and Singh S: Interleukin-8 is a key mediator of FKBP51-induced melanoma growth, angiogenesis and metastasis. Br J Cancer. 112:1772–1781. 2015. View Article : Google Scholar : PubMed/NCBI
11	Nakanishi M, Morita Y, Hata K and Muragaki Y: Acidic microenvironments induce lymphangiogenesis and IL-8 production via TRPV1 activation in human lymphatic endothelial cells. Exp Cell Res. 345:180–189. 2016. View Article : Google Scholar : PubMed/NCBI
12	Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD and Julius D: The capsaicin receptor: A heat-activated ion channel in the pain pathway. Nature. 389:816–824. 1997. View Article : Google Scholar : PubMed/NCBI
13	Nakanishi M, Hata K, Nagayama T, Sakurai T, Nishisho T, Wakabayashi H, Hiraga T, Ebisu S and Yoneda T: Acid activation of Trpv1 leads to an up-regulation of calcitonin gene-related peptide expression in dorsal root ganglion neurons via the CaMK-CREB cascade: A potential mechanism of inflammatory pain. Mol Biol Cell. 21:2568–2577. 2010. View Article : Google Scholar : PubMed/NCBI
14	Yoneda T, Hata K, Nakanishi M, Nagae M, Nagayama T, Wakabayashi H, Nishisho T, Sakurai T and Hiraga T: Involvement of acidic microenvironment in the pathophysiology of cancer-associated bone pain. Bone. 48:100–105. 2011. View Article : Google Scholar : PubMed/NCBI
15	Sherwood TW, Frey EN and Askwith CC: Structure and activity of the acid-sensing ion channels. Am J Physiol Cell Physiol. 303:C699–C710. 2012. View Article : Google Scholar : PubMed/NCBI
16	Wu Y, Gao B, Xiong Q, Wang Y, Huang D and Wu W-N: Acid sensing ion channels contribute to the effect of extracellular acidosis in proliferation and migration of A549 cells. Tumour Biol. 39:10104283177057502017. View Article : Google Scholar : PubMed/NCBI
17	Zhu S, Zhou HY, Deng SC, Deng SJ, He C, Li X, Chen J-Y, Jin Y, Hu Z-L, Wang F, et al: ASIC1 and ASIC3 contribute to acidity-induced EMT of pancreatic cancer through activating Ca(2+)/RhoA pathway. Cell Death Dis. 8:e28062017. View Article : Google Scholar : PubMed/NCBI
18	Rooj AK, McNicholas CM, Bartoszewski R, Bebok Z, Benos DJ and Fuller CM: Glioma-specific cation conductance regulates migration and cell cycle progression. J Biol Chem. 287:4053–4065. 2012. View Article : Google Scholar : PubMed/NCBI
19	Tian Y, Bresenitz P, Reska A, El Moussaoui L, Beier CP and Gründer S: Glioblastoma cancer stem cell lines express functional acid sensing ion channels ASIC1a and ASIC3. Sci Rep. 7:136742017. View Article : Google Scholar : PubMed/NCBI
20	Berdiev BK, Xia J, McLean LA, Markert JM, Gillespie GY, Mapstone TB, Naren AP, Jovov B, Bubien JK, Ji H-L, et al: Acid-sensing ion channels in malignant gliomas. J Biol Chem. 278:15023–15034. 2003. View Article : Google Scholar : PubMed/NCBI
21	Kapoor N, Bartoszewski R, Qadri YJ, Bebok Z, Bubien JK, Fuller CM and Benos DJ: Knockdown of ASIC1 and epithelial sodium channel subunits inhibits glioblastoma whole cell current and cell migration. J Biol Chem. 284:24526–24541. 2009. View Article : Google Scholar : PubMed/NCBI
22	Gatenby RA and Gawlinski ET: A reaction-diffusion model of cancer invasion. Cancer Res. 56:5745–5753. 1996.PubMed/NCBI
23	Stubbs M, McSheehy PM, Griffiths JR and Bashford CL: Causes and consequence of tumour acidity and implications for treatment. Mol Med Today. 6:15–19. 2000. View Article : Google Scholar : PubMed/NCBI
24	Hashim AI, Zhang X, Wojtkowiak JW, Martinez GV and Gillies RJ: Imaging pH and metastasis. NMR Biomed. 24:582–591. 2011. View Article : Google Scholar : PubMed/NCBI
25	Wemmie JA, Taugher RJ and Kreple CJ: Acid-sensing ion channels in pain and disease. Nat Rev Neurosci. 14:461–471. 2013. View Article : Google Scholar : PubMed/NCBI
26	Matsuo T and Sadzuka Y: Extracellular acidification by lactic acid suppresses glucose deprivation-induced cell death and autophagy in B16 melanoma cells. Biochem Biophys Res Commun. 496:1357–1361. 2018. View Article : Google Scholar : PubMed/NCBI
27	de la Cruz-López KG, Castro-Muñoz LJ, Reyes-Hernández DO, García-Carrancá A and Manzo-Merino J: Lactate in the regulation of tumor microenvironment and therapeutic approaches. Front Oncol. 9:11432019. View Article : Google Scholar : PubMed/NCBI
28	Chen B, Liu J, Ho TT, Ding X and Mo YY: ERK-mediated NF-kappaB activation through ASIC1 in response to acidosis. Oncogenesis. 5:e2792016. View Article : Google Scholar : PubMed/NCBI
29	Böhme I and Bosserhoff A: Extracellular acidosis triggers a senescence-like phenotype in human melanoma cells. Pigment Cell Melanoma Res. 33:41–51. 2020. View Article : Google Scholar : PubMed/NCBI
30	Wojtkowiak JW, Rothberg JM, Kumar V, Schramm KJ, Haller E, Proemsey JB, Lloyd MC, Sloane BF and Gillies RJ: Chronic autophagy is a cellular adaptation to tumor acidic pH microenvironments. Cancer Res. 72:3938–3947. 2012. View Article : Google Scholar : PubMed/NCBI
31	Végran F, Boidot R, Michiels C, Sonveaux P and Feron O: Lactate influx through the endothelial cell monocarboxylate transporter MCT1 supports an NF-κB/IL-8 pathway that drives tumor angiogenesis. Cancer Res. 71:2550–2560. 2011. View Article : Google Scholar : PubMed/NCBI
32	Brat DJ, Bellail AC and Van Meir EG: The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis. Neuro-oncol. 7:122–133. 2005. View Article : Google Scholar : PubMed/NCBI
33	Pecze L, Josvay K, Blum W, Petrovics G, Vizler C, Oláh Z and Schwaller B: Activation of endogenous TRPV1 fails to induce overstimulation-based cytotoxicity in breast and prostate cancer cells but not in pain-sensing neurons. Biochim Biophys Acta. 1863:2054–2064. 2016. View Article : Google Scholar : PubMed/NCBI
34	Weber LV, Al-Refae K, Wölk G, Bonatz G, Altmüller J, Becker C, Gisselmann G and Hatt H: Expression and functionality of TRPV1 in breast cancer cells. Breast Cancer (Dove Med Press). 8:243–252. 2016.PubMed/NCBI
35	Lozano C, Córdova C, Marchant I, Zúñiga R, Ochova P, Ramírez-Barrantes R, González-Arriagada WA, Rodriguez B and Olivero P: Intracellular aggregated TRPV1 is associated with lower survival in breast cancer patients. Breast Cancer (Dove Med Press). 10:161–168. 2018.PubMed/NCBI
36	So CL, Milevskiy MJG and Monteith GR: Transient receptor potential cation channel subfamily V and breast cancer. Lab Invest. 100:199–206. 2020. View Article : Google Scholar : PubMed/NCBI
37	Singh LS, Berk M, Oates R, Zhao Z, Tan H, Jiang Y, Zhou A, Kirmani K, Steinmetz R, Lindner D, et al: Ovarian cancer G protein-coupled receptor 1, a new metastasis suppressor gene in prostate cancer. J Natl Cancer Inst. 99:1313–1327. 2007. View Article : Google Scholar : PubMed/NCBI
38	Li J, Guo B, Wang J, Cheng X, Xu Y and Sang J: Ovarian cancer G protein coupled receptor 1 suppresses cell migration of MCF7 breast cancer cells via a Gα_12/13-Rho-Rac1 pathway. J Mol Signal. 8:62013. View Article : Google Scholar : PubMed/NCBI
39	Zhang J, Che L, Sun W, Shang J, Hao M and Tian M: Correlation of OGR1 with proliferation and apoptosis of breast cancer cells. Oncol Lett. 17:4335–4340. 2019.PubMed/NCBI
40	Gupta SC, Singh R, Asters M, Liu J, Zhang X, Pabbidi MR, Watabe K and Mo Y-Y: Regulation of breast tumorigenesis through acid sensors. Oncogene. 35:4102–4111. 2016. View Article : Google Scholar : PubMed/NCBI
41	García-Cañaveras JC, Chen L and Rabinowitz JD: The tumor metabolic microenvironment: Lessons from lactate. Cancer Res. 79:3155–3162. 2019. View Article : Google Scholar : PubMed/NCBI
42	Kolesnik DL, Pyaskovskaya ON and Solyanik GI: Impact of lactic acidosis on the survival of Lewis lung carcinoma cells. Exp Oncol. 39:112–116. 2017. View Article : Google Scholar : PubMed/NCBI
43	Romero-Garcia S, Prado-Garcia H, Valencia-Camargo AD and Alvarez-Pulido A: Lactic acidosis promotes mitochondrial biogenesis in lung adenocarcinoma cells, supporting proliferation under normoxia or survival under hypoxia. Front Oncol. 9:10532019. View Article : Google Scholar : PubMed/NCBI
44	Pinheiro C, Garcia EA, Morais-Santon F, Scapulatempo-Neto C, Mafra A, Steenbergen RDM, Boccardo E, Villa LL, Baltazar F and Longatto-Filho A: Lactate transporters and vascular factors in HPV-induced squamous cell carcinoma of the uterine cervix. BMC Cancer. 14:7512014. View Article : Google Scholar : PubMed/NCBI
45	Roland CL, Arumugam T, Deng D, Liu SH, Philip B, Gomez S, Burns WR, Ramachandran V, Wang H, Cruz-Monserrate Z, et al: Cell surface lactate receptor GPR81 is crucial for cancer cell survival. Cancer Res. 74:5301–5310. 2014. View Article : Google Scholar : PubMed/NCBI
46	Chen P, Zuo H, Xiong H, Kolar MJ, Chu Q, Saghatelian A, Siegwart DJ and Wan Y: Gpr132 sensing of lactate mediates tumor-macrophage interplay to promote breast cancer metastasis. Proc Natl Acad Sci USA. 114:580–585. 2017. View Article : Google Scholar : PubMed/NCBI