S100A8 facilitates cholangiocarcinoma metastasis via upregulation of VEGF through TLR4/NF‑κB pathway activation Corrigendum in /10.3892/ijo.2020.4977

Pan,Shuguang; Hu,Ying; Hu,Mengjia; Xu,Yang; Chen,Mo; Du,Changhong; Cui,Jinchi; Zheng,Ping; Lai,Jiejuan; Zhang,Yujun; Bai,Jie; Jiang,Peng; Zhu,Jin; He,Yu; Wang,Junping

doi:10.3892/ijo.2019.4907

S100A8 facilitates cholangiocarcinoma metastasis via upregulation of VEGF through TLR4/NF‑κB pathway activation

Corrigendum in: /10.3892/ijo.2020.4977

Authors:
- Shuguang Pan
- Ying Hu
- Mengjia Hu
- Yang Xu
- Mo Chen
- Changhong Du
- Jinchi Cui
- Ping Zheng
- Jiejuan Lai
- Yujun Zhang
- Jie Bai
- Peng Jiang
- Jin Zhu
- Yu He
- Junping Wang
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Affiliations: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Centre for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, P.R. China, Oncology Department, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China, Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China
Published online on: October 30, 2019 https://doi.org/10.3892/ijo.2019.4907
Pages: 101-112
Copyright: © Pan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

A growing body of evidence indicates that S100 calcium‑binding protein A8 (S100A8) is frequently overexpressed in malignant tumor tissues and regulates tumor progression; however, the role of S100A8 in cholangiocarcinoma (CCA) remains unclear. The present study demonstrated that the protein expression of S100A8 was significantly higher in pathological tissues compared with adjacent normal tissues from patients with CCA. In addition, S100A8 expression was significantly associated with differentiation, lymph node metastasis and poor prognosis in patients following surgical resection of CCA. Furthermore, both in vitro and in vivo experiments revealed that overexpression of S100A6 promoted, while S100A8 knockdown attenuated, the migration and metastasis of CCA cells. Of note, the present results indicated that S100A8 promoted the CCA tumor cell‑induced migration of vascular endothelial cells. Finally, S100A8 was demonstrated to positively regulate the expression of vascular endothelial growth factor (VEGF) in CCA cells, which was mediated by activation of the Toll‑like receptor 4 (TLR4)/NF‑κB pathway. In conclusion, the present study demonstrated that S100A8 had an important role in facilitating CCA cell migration and metastasis via upregulation of VEGF expression by activating the TLR4/NF‑κB pathway. These findings may provide a novel target for CCA treatment.

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1	Razumilava N and Gores GJ: Cholangiocarcinoma. Lancet. 383:2168–2179. 2014. View Article : Google Scholar : PubMed/NCBI
2	Tyson GL and El-Serag HB: Risk factors for cholangiocarcinoma. Hepatology. 54:173–184. 2011. View Article : Google Scholar : PubMed/NCBI
3	Khan SA, Davidson BR, Goldin RD, Heaton N, Karani J, Pereira SP, Rosenberg WM, Tait P, Taylor-Robinson SD, Thillainayagam AV, et al: Guidelines for the diagnosis and treatment of cholangiocarcinoma: An update. Gut. 61:1657–1669. 2012. View Article : Google Scholar : PubMed/NCBI
4	Lim SY, Yuzhalin AE, Gordon-Weeks AN and Muschel RJ: Tumor-infiltrating monocytes/macrophages promote tumor invasion and migration by upregulating S100A8 and S100A9 expression in cancer cells. Oncogene. 35:5735–5745. 2016. View Article : Google Scholar : PubMed/NCBI
5	Yu LX, Yan L, Yang W, Wu FQ, Ling Y, Chen SZ, Tang L, Tan YX, Cao D, Wu MC, et al: Platelets promote tumour metastasis via interaction between TLR4 and tumour cell-released high-mobility group box1 protein. Nat Commun. 5:52562014. View Article : Google Scholar : PubMed/NCBI
6	Gupta GP and Massagué J: Cancer metastasis: Building a framework. Cell. 127:679–695. 2006. View Article : Google Scholar : PubMed/NCBI
7	Brantley-Sieders DM, Fang WB, Hwang Y, Hicks D and Chen J: Ephrin-A1 facilitates mammary tumor metastasis through an angiogenesis-dependent mechanism mediated by EphA receptor and vascular endothelial growth factor in mice. Cancer Res. 66:10315–10324. 2006. View Article : Google Scholar : PubMed/NCBI
8	Kalinsky K, Mayer JA, Xu X, Pham T, Wong KL, Villarin E, Pircher TJ, Brown M, Maurer MA and Bischoff FZ: Correlation of hormone receptor status between circulating tumor cells, primary tumor, and metastasis in breast cancer patients. Clin Transl Oncol. 17:539–546. 2015. View Article : Google Scholar : PubMed/NCBI
9	Valastyan S and Weinberg RA: Tumor metastasis: Molecular insights and evolving paradigms. Cell. 147:275–292. 2011. View Article : Google Scholar : PubMed/NCBI
10	Srikrishna G: S100A8 and S100A9: New insights into their roles in malignancy. J Innate Immun. 4:31–40. 2012. View Article : Google Scholar :
11	Leukert N, Vogl T, Strupat K, Reichelt R, Sorg C and Roth J: Calcium-dependent tetramer formation of S100A8 and S100A9 is essential for biological activity. J Mol Biol. 359:961–972. 2006. View Article : Google Scholar : PubMed/NCBI
12	Lim SY, Raftery MJ and Geczy CL: Oxidative modifications of DAMPs suppress inflammation: The case for S100A8 and S100A9. Antioxid Redox Signal. 15:2235–2248. 2011. View Article : Google Scholar
13	Porta C, Larghi P, Rimoldi M, Totaro MG, Allavena P, Mantovani A and Sica A: Cellular and molecular pathways linking inflammation and cancer. Immunobiology. 214:761–777. 2009. View Article : Google Scholar : PubMed/NCBI
14	Hiratsuka S, Watanabe A, Sakurai Y, Akashi-Takamura S, Ishibashi S, Miyake K, Shibuya M, Akira S, Aburatani H and Maru Y: The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. Nat Cell Biol. 10:1349–1355. 2008. View Article : Google Scholar : PubMed/NCBI
15	Kapanadze T, Gamrekelashvili J, Ma C, Chan C, Zhao F, Hewitt S, Zender L, Kapoor V, Felsher DW, Manns MP, et al: Regulation of accumulation and function of myeloid derived suppressor cells in different murine models of hepatocellular carcinoma. J Hepatol. 59:1007–1013. 2013. View Article : Google Scholar : PubMed/NCBI
16	Hamerlik P, Lathia JD, Rasmussen R, Wu Q, Bartkova J, Lee M, Moudry P, Bartek J Jr, Fischer W, Lukas J, et al: Autocrine VEGF-VEGFR2-Neuropilin-1 signaling promotes glioma stem-like cell viability and tumor growth. J Exp Med. 209:507–520. 2012. View Article : Google Scholar : PubMed/NCBI
17	Chatterjee S, Heukamp LC, Siobal M, Schöttle J, Wieczorek C, Peifer M, Frasca D, Koker M, König K, Meder L, et al: Tumor VEGF:VEGFR2 autocrine feed-forward loop triggers angiogenesis in lung cancer. J Clin Invest. 123:1732–1740. 2013. View Article : Google Scholar : PubMed/NCBI
18	Alessi C, Scapulatempo Neto C, Viana CR and Vazquez VL: PD-1/PD-L1 and VEGF-A/VEGF-C expression in lymph node microenvironment and association with melanoma metastasis and survival. Melanoma Res. 27:565–572. 2017. View Article : Google Scholar : PubMed/NCBI
19	Yang X, Zhang Y, Hosaka K, Andersson P, Wang J, Tholander F, Cao Z, Morikawa H, Tegnér J, Yang Y, et al: VEGF-B promotes cancer metastasis through a VEGF-A-independent mechanism and serves as a marker of poor prognosis for cancer patients. Proc Natl Acad Sci USA. 112:E2900–E2909. 2015. View Article : Google Scholar : PubMed/NCBI
20	Gay LJ and Felding-Habermann B: Contribution of platelets to tumour metastasis. Nat Rev Cancer. 11:123–134. 2011. View Article : Google Scholar : PubMed/NCBI
21	Dehghani S, Nosrati R, Yousefi M, Nezami A, Soltani F, Taghdisi SM, Abnous K, Alibolandi M and Ramezani M: Aptamer-based biosensors and nanosensors for the detection of vascular endothelial growth factor (VEGF): A review. Biosens Bioelectron. 110:23–37. 2018. View Article : Google Scholar : PubMed/NCBI
22	Huang D, Song SJ, Wu ZZ, Wu W, Cui XY, Chen JN, Zeng MS and Su SC: Epstein-barr virus-induced VEGF and GM-CSF drive nasopharyngeal carcinoma metastasis via recruitment and activation of macrophages. Cancer Res. 77:3591–3604. 2017. View Article : Google Scholar : PubMed/NCBI
23	Zhang Z, Ji S, Zhang B, Liu J, Qin Y, Xu J and Yu X: Role of angiogenesis in pancreatic cancer biology and therapy. Biomed Pharmacother. 108:1135–1140. 2018. View Article : Google Scholar : PubMed/NCBI
24	Van Dreden P, Epsilonlalamy I and Gerotziafas GT: The role of tissue factor in cancer-related hypercoagulability, tumor growth, angiogenesis and metastasis and future therapeutic strategies. Crit Rev Oncog. 22:219–248. 2017. View Article : Google Scholar : PubMed/NCBI
25	Long T, Liu Z, Shang J, Zhou X, Yu S, Tian H and Bao Y: Polygonatum sibiricum polysaccharides play anti-cancer effect through TLR4-MAPK/NF-κB signaling pathways. Int J Biol Macromol. 111:813–821. 2018. View Article : Google Scholar : PubMed/NCBI
26	Gu JW, Young E, Busby B, Covington J and Johnson JW: Oral administration of pyrrolidine dithiocarbamate (PDTC) inhibits VEGF expression, tumor angiogenesis, and growth of breast cancer in female mice. Cancer Biol Ther. 8:514–521. 2009. View Article : Google Scholar : PubMed/NCBI
27	Gan L, Pan S, Cui J, Bai J, Jiang P and He Y: Functional analysis of the correlation between ABCB11 gene mutation and primary intrahepatic stone. Mol Med Rep. 19:195–204. 2019.
28	Pan S, Li X, Jiang P, Jiang Y, Shuai L, He Y and Li Z: Variations of ABCB4 and ABCB11 genes are associated with primary intrahepatic stones. Mol Med Rep. 11:434–446. 2015. View Article : Google Scholar
29	Zhang B, Wang D, Ji TF, Shi L and Yu JL: Overexpression of lncRNA ANRIL up-regulates VEGF expression and promotes angiogenesis of diabetes mellitus combined with cerebral infarction by activating NF-κB signaling pathway in a rat model. Oncotarget. 8:17347–17359. 2017.PubMed/NCBI
30	Labelle M and Hynes RO: The initial hours of metastasis: The importance of cooperative host-tumor cell interactions during hematogenous dissemination. Cancer Discov. 2:1091–1099. 2012. View Article : Google Scholar : PubMed/NCBI
31	Shin JM, Park JH, Kim HJ, Park IH and Lee HM: Cigarette smoke extract increases vascular endothelial growth factor production via TLR4/ROS/MAPKs/NF-kappaB pathway in nasal fibroblast. Am J Rhinol Allergy. 31:78–84. 2017. View Article : Google Scholar : PubMed/NCBI
32	Naruishi K and Nagata T: Biological effects of interleukin-6 on Gingival Fibroblasts: Cytokine regulation in periodontitis. J Cell Physiol. 233:6393–6400. 2018. View Article : Google Scholar : PubMed/NCBI
33	Sonbare DJ: Influence of surgical margins on outcome in patients with intrahepatic cholangiocarcinoma: A multicenter study by the AFC-IHCC-2009 Study Group. Ann Surg. 259:e362014. View Article : Google Scholar
34	Lau SH and Lau WY: Current therapy of hilar cholangiocarcinoma. Hepatobiliary Pancreat Dis Int. 11:12–17. 2012. View Article : Google Scholar : PubMed/NCBI
35	Yin DL, Liang YJ, Zheng TS, Song RP, Wang JB, Sun BS, Pan SH, Qu LD, Liu JR, Jiang HC and Liu LX: EF24 inhibits tumor growth and metastasis via suppressing NF-kappaB dependent pathways in human cholangiocarcinoma. Sci Rep. 6:321672016. View Article : Google Scholar : PubMed/NCBI
36	Ghavami S, Rashedi I, Dattilo BM, Eshraghi M, Chazin WJ, Hashemi M, Wesselborg S, Kerkhoff C and Los M: S100A8/A9 at low concentration promotes tumor cell growth via RAGE ligation and MAP kinase-dependent pathway. J Leukoc Biol. 83:1484–1492. 2008. View Article : Google Scholar : PubMed/NCBI
37	Shabani F, Farasat A, Mahdavi M and Gheibi N: Calprotectin (S100A8/S100A9): A key protein between inflammation and cancer. Inflamm Res. 67:801–812. 2018. View Article : Google Scholar : PubMed/NCBI
38	Miller P, Kidwell KM, Thomas D, Sabel M, Rae JM, Hayes DF, Hudson BI, El-Ashry D and Lippman ME: Elevated S100A8 protein expression in breast cancer cells and breast tumor stroma is prognostic of poor disease outcome. Breast Cancer Res Treat. 166:85–94. 2017. View Article : Google Scholar : PubMed/NCBI
39	Steinckwich N, Schenten V, Melchior C, Bréchard S and Tschirhart EJ: An essential role of STIM1, Orai1, and S100A8-A9 proteins for Ca2+ signaling and FcgammaR-mediated phagosomal oxidative activity. J Immunol. 186:2182–2191. 2011. View Article : Google Scholar : PubMed/NCBI
40	Ieguchi K, Omori T, Komatsu A, Tomita T, Deguchi A and Maru Y: Ephrin-A1 expression induced by S100A8 is mediated by the toll-like receptor 4. Biochem Biophys Res Commun. 440:623–629. 2013. View Article : Google Scholar : PubMed/NCBI
41	Tanriover G, Eyinc MB, Aliyev E, Dilmac S and Erin N: Presence of S100A8/Gr1-positive myeloid-derived suppressor cells in primary tumors and visceral organs invaded by breast carcinoma cells. Clin Breast Cancer. 18:e1067–e1076. 2018. View Article : Google Scholar : PubMed/NCBI
42	Weis SM and Cheresh DA: Tumor angiogenesis: Molecular pathways and therapeutic targets. Nat Med. 17:1359–1370. 2011. View Article : Google Scholar : PubMed/NCBI
43	Gacche RN and Meshram RJ: Angiogenic factors as potential drug target: Efficacy and limitations of anti-angiogenic therapy. Biochim Biophys Acta. 1846:161–179. 2014.PubMed/NCBI
44	Viallard C and Larrivée B: Tumor angiogenesis and vascular normalization: Alternative therapeutic targets. Angiogenesis. 20:409–426. 2017. View Article : Google Scholar : PubMed/NCBI
45	Liang W and Ferrara N: The Complex role of neutrophils in tumor angiogenesis and metastasis. Cancer Immunol Res. 4:83–91. 2016. View Article : Google Scholar : PubMed/NCBI
46	Li C, Li S, Jia C, Yang L, Song Z and Wang Y: Low concentration of S100A8/9 promotes angiogenesis-related activity of vascular endothelial cells: Bridges among inflammation, angiogenesis, and tumorigenesis? Mediators Inflamm. 2012:2485742012. View Article : Google Scholar : PubMed/NCBI
47	Viemann D, Strey A, Janning A, Jurk K, Klimmek K, Vogl T, Hirono K, Ichida F, Foell D, Kehrel B, et al: Myeloid-related proteins 8 and 14 induce a specific inflammatory response in human microvascular endothelial cells. Blood. 105:2955–2962. 2005. View Article : Google Scholar
48	Viemann D, Barczyk K, Vogl T, Fischer U, Sunderkötter C, Schulze-Osthoff K and Roth J: MRP8/MRP14 impairs endothelial integrity and induces a caspase-dependent and -independent cell death program. Blood. 109:2453–2460. 2007. View Article : Google Scholar
49	Li Y, Xie G, Li L, Jiang Z, Yue Z and Pan Z: The effect of TLR4/MyD88/NF-κB signaling pathway on proliferation and apoptosis in human nasopharyngeal carcinoma 5-8F cells induced by LPS. Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 29:1012–1015. 2015.In Chinese.
50	Jiang N, Xie F, Guo Q, Li MQ, Xiao J and Sui L: Toll-like receptor 4 promotes proliferation and apoptosis resistance in human papillomavirus-related cervical cancer cells through the Toll-like receptor 4/nuclear factor-κB pathway. Tumour Biol. 39:10104283177105862017. View Article : Google Scholar
51	O'Driscoll CM, Lima MP, Kaufmann WE and Bressler JP: Methyl CpG binding protein 2 deficiency enhances expression of inflammatory cytokines by sustaining NF-κB signaling in myeloid derived cells. J Neuroimmunol. 283:23–29. 2015. View Article : Google Scholar : PubMed/NCBI
52	Low P, Clark AM, Chou TC, Chang TC, Reynolds M and Ralph SJ: Immunomodulatory activity of Melaleuca alternifolia concentrate (MAC): Inhibition of LPS-induced NF-κB activation and cytokine production in myeloid cell lines. Int Immunopharmacol. 26:257–264. 2015. View Article : Google Scholar : PubMed/NCBI