Skip to main content
Top
Published in: Cancer Cell International 1/2017

Open Access 01-12-2017 | Primary Research

PA-MSHA induces apoptosis and suppresses metastasis by tumor associated macrophages in bladder cancer cells

Authors: Jianjun Liu, Xiaoyu Duan

Published in: Cancer Cell International | Issue 1/2017

Login to get access

Abstract

Background

The aim of the present study was to investigate effects of Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA) on the inhibition of the proliferation of bladder cancer cell lines and to further define its functional mechanisms.

Methods

A rat model of bladder tumor was induced by intravesical N-methyl-N nitrosourea. The dynamic growth of tumor was measured by whole-body fluorescent imaging system. Morphological analysis was observed by hematoxylin–eosin staining and microscopic examination. The expression of Caspase 3 and E-Ca were detected by immunohistochemistry technique. Macrophages were separated by flow cytometry. The expression of cytokines was measured by qRT-PCR and western blot. Apoptosis ability was conducted by means of annexin V and propidium iodide. The abilities of invasion and migration were determined by transwell migration assay and scratch assay.

Results

PA-MSHA and PA-MSHA + Fisetin groups inhibited the growth of tumor and increased the ratio of M1/M2. For one thing, PA-MSHA suppressed the invasive ability of the bladder tumor cell and promoted bladder tumor cell apoptosis. For another, it facilitated the expression of M1 cytokines and reduced expression of M2 cytokines. Furthermore, treated with PA-MSHA, mouse M1 phagocytosis rates were higher than that of M2 macrophages for bladder cancer lines.

Conclusions

The data revealed that PA-MSHA might promote apoptosis and inhibit proliferation, invasion and migration of mouse bladder cancer cells by inducing M1 polarization.
Literature
1.
go back to reference Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. A Cancer J Clin. 2013;63(1):11–30.CrossRef Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. A Cancer J Clin. 2013;63(1):11–30.CrossRef
2.
go back to reference Jemal A, Bray F, Center MM, Ferlay JJ, Ward E, Forman D. Global cancer statistics. Cancer J Clin. 2011;61(2):69–90.CrossRef Jemal A, Bray F, Center MM, Ferlay JJ, Ward E, Forman D. Global cancer statistics. Cancer J Clin. 2011;61(2):69–90.CrossRef
3.
go back to reference Wirth M, Plattner VE, Gabor F. Strategies to improve drug delivery in bladder cancer therapy. Exp Opin Drug Deliv. 2009;6(6):727–44.CrossRef Wirth M, Plattner VE, Gabor F. Strategies to improve drug delivery in bladder cancer therapy. Exp Opin Drug Deliv. 2009;6(6):727–44.CrossRef
4.
go back to reference Mansoor M, Ali S, Fasihuddin Q, Baloch MU. Superficial bladder tumours: recurrence and progression. J Coll Phys Surg Pak. 2011;21(3):157–60. Mansoor M, Ali S, Fasihuddin Q, Baloch MU. Superficial bladder tumours: recurrence and progression. J Coll Phys Surg Pak. 2011;21(3):157–60.
5.
go back to reference Pasin E, Josephson DY, Mitra AP, Cote RJ, Stein JP. Superficial bladder cancer: an update on etiology, molecular development, classification, and natural history. Rev Urol. 2008;10(1):31–43.PubMedPubMedCentral Pasin E, Josephson DY, Mitra AP, Cote RJ, Stein JP. Superficial bladder cancer: an update on etiology, molecular development, classification, and natural history. Rev Urol. 2008;10(1):31–43.PubMedPubMedCentral
6.
go back to reference Herr HW. High-risk superficial bladder cancer: transurethral resection alone in selected patients with T1 tumor. J Urol. 1997;160(5):1934.CrossRef Herr HW. High-risk superficial bladder cancer: transurethral resection alone in selected patients with T1 tumor. J Urol. 1997;160(5):1934.CrossRef
7.
go back to reference Yun SJ, Kim WJ. Role of the epithelial-mesenchymal transition in bladder cancer: from prognosis to therapeutic target. Korean J Urol. 2013;54(10):645–50.CrossRefPubMedPubMedCentral Yun SJ, Kim WJ. Role of the epithelial-mesenchymal transition in bladder cancer: from prognosis to therapeutic target. Korean J Urol. 2013;54(10):645–50.CrossRefPubMedPubMedCentral
8.
go back to reference Fiorito C, Gontero P. Adverse events after intravesical therapy: are we always ready to recognize and prevent them? Urologia. 2013;80(Suppl 21):27–32.CrossRefPubMed Fiorito C, Gontero P. Adverse events after intravesical therapy: are we always ready to recognize and prevent them? Urologia. 2013;80(Suppl 21):27–32.CrossRefPubMed
9.
go back to reference Griffin JG, Holzbeierlein J. Side effects of perioperative intravesical treatment and treatment strategies for these side effects. Urol Clin N Am. 2013;40(2):197–210.CrossRef Griffin JG, Holzbeierlein J. Side effects of perioperative intravesical treatment and treatment strategies for these side effects. Urol Clin N Am. 2013;40(2):197–210.CrossRef
10.
go back to reference Mead GM, Russell M, Clark P, Harland SJ, Harper PG, Cowan R, Roberts JT, Uscinska BM, Griffiths GO, Parmar MK. A randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced transitional cell carcinoma: results and a report on prognostic factors in a Medical Research Council study, MRC Advanced Bladder. Brit J Cancer. 1998;78(8):1067–75.CrossRefPubMedPubMedCentral Mead GM, Russell M, Clark P, Harland SJ, Harper PG, Cowan R, Roberts JT, Uscinska BM, Griffiths GO, Parmar MK. A randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced transitional cell carcinoma: results and a report on prognostic factors in a Medical Research Council study, MRC Advanced Bladder. Brit J Cancer. 1998;78(8):1067–75.CrossRefPubMedPubMedCentral
11.
go back to reference Lee N, Ahn B, Jung SB, Kim YG, Kim H, Park WJ. Conformation-dependent antibody response to Pseudomonas aeruginosa outer membrane proteins induced by immunization in humans. FEMS Immunol Med Microbiol. 2000;27(1):79–85.CrossRefPubMed Lee N, Ahn B, Jung SB, Kim YG, Kim H, Park WJ. Conformation-dependent antibody response to Pseudomonas aeruginosa outer membrane proteins induced by immunization in humans. FEMS Immunol Med Microbiol. 2000;27(1):79–85.CrossRefPubMed
12.
go back to reference Porwoll JM, Gebel HM, Rodey GE, Markham RB. In vitro response of human T cells to Pseudomonas aeruginosa. Infect Immun. 1983;40(2):670–4.PubMedPubMedCentral Porwoll JM, Gebel HM, Rodey GE, Markham RB. In vitro response of human T cells to Pseudomonas aeruginosa. Infect Immun. 1983;40(2):670–4.PubMedPubMedCentral
13.
go back to reference Cheng GZ, Jia CX, Yang HR. Studies on mechanism of immunization against recurrent urinary tract infection with MSHA—piliated strain vaccine of Pseudomonas aeruginosa. Chin J Microecol. 2000;12:331–3. Cheng GZ, Jia CX, Yang HR. Studies on mechanism of immunization against recurrent urinary tract infection with MSHA—piliated strain vaccine of Pseudomonas aeruginosa. Chin J Microecol. 2000;12:331–3.
14.
go back to reference Sun W, Hongwen FU, Liu N. Clinical investigation of PA-MSHA strain vaccine on the improvement of immune functions of cancer patients. Chin J Microbiol Immunol. 2000;20(4):373–6. Sun W, Hongwen FU, Liu N. Clinical investigation of PA-MSHA strain vaccine on the improvement of immune functions of cancer patients. Chin J Microbiol Immunol. 2000;20(4):373–6.
15.
go back to reference Li Z, Hao D, Zhang H, Ren L, Yang Y, Li L, Chai J, Zhou X, Fu L. A clinical study on PA-MSHA vaccine used for adjuvant therapy of lymphoma and lung cancer. Hua xi yi ke da xue xue bao. 2000;31(3):334–7.PubMed Li Z, Hao D, Zhang H, Ren L, Yang Y, Li L, Chai J, Zhou X, Fu L. A clinical study on PA-MSHA vaccine used for adjuvant therapy of lymphoma and lung cancer. Hua xi yi ke da xue xue bao. 2000;31(3):334–7.PubMed
16.
go back to reference Cao Z, Shi L, Li Y, Wang J, Wang D, Wang G, Sun B, Mu L, Yang M, Li H. Pseudomonas aeruginosa: mannose sensitive hemagglutinin inhibits the growth of human hepatocarcinoma cells via mannose-mediated apoptosis. Digest Dis Sci. 2009;54(10):2118–27.CrossRefPubMed Cao Z, Shi L, Li Y, Wang J, Wang D, Wang G, Sun B, Mu L, Yang M, Li H. Pseudomonas aeruginosa: mannose sensitive hemagglutinin inhibits the growth of human hepatocarcinoma cells via mannose-mediated apoptosis. Digest Dis Sci. 2009;54(10):2118–27.CrossRefPubMed
17.
go back to reference Liu ZB, Hou YF, Di GH, Wu J, Shen ZZ, Shao ZM. PA-MSHA inhibits proliferation and induces apoptosis through the up-regulation and activation of caspases in the human breast cancer cell lines. J Cell Biochem. 2009;108(1):195–206.CrossRefPubMed Liu ZB, Hou YF, Di GH, Wu J, Shen ZZ, Shao ZM. PA-MSHA inhibits proliferation and induces apoptosis through the up-regulation and activation of caspases in the human breast cancer cell lines. J Cell Biochem. 2009;108(1):195–206.CrossRefPubMed
18.
go back to reference Wang J, Wu D, Chen L. Pseudomonas aeruginosa vaccine inhibits the proliferation of human nasopharyngeal cancer cells in vitro. Nan fang yi ke da xue xue bao. 2012;32(4):544–7.PubMed Wang J, Wu D, Chen L. Pseudomonas aeruginosa vaccine inhibits the proliferation of human nasopharyngeal cancer cells in vitro. Nan fang yi ke da xue xue bao. 2012;32(4):544–7.PubMed
19.
go back to reference Wei L, Hua L, Hui C, Feng-Rong YU. Effects of PA-MSHA vaccine on gastric cancer cells in vitro. Chin J Cancer Prev Treat. 2008;15(18):1381–5. Wei L, Hua L, Hui C, Feng-Rong YU. Effects of PA-MSHA vaccine on gastric cancer cells in vitro. Chin J Cancer Prev Treat. 2008;15(18):1381–5.
20.
go back to reference Wang C, Hu Z, Zhu Z, Zhang X, Wei Z, Zhang Y, Hu D, Cai Q. The MSHA strain of Pseudomonas aeruginosa (PA-MSHA) inhibits gastric carcinoma progression by inducing M1 macrophage polarization. Tumor Biol. 2016;37(5):1–9.CrossRef Wang C, Hu Z, Zhu Z, Zhang X, Wei Z, Zhang Y, Hu D, Cai Q. The MSHA strain of Pseudomonas aeruginosa (PA-MSHA) inhibits gastric carcinoma progression by inducing M1 macrophage polarization. Tumor Biol. 2016;37(5):1–9.CrossRef
21.
go back to reference Zhang M, Gregor H, Kahn SA, Azad TD, Sharareh G, Xu CY, Liu J, Achrol AS, Chase R, Pia S. Anti-CD47 treatment stimulates phagocytosis of glioblastoma by M1 and M2 polarized macrophages and promotes M1 polarized macrophages in vivo. PLoS ONE. 2016;11(4):e0153550.CrossRefPubMedPubMedCentral Zhang M, Gregor H, Kahn SA, Azad TD, Sharareh G, Xu CY, Liu J, Achrol AS, Chase R, Pia S. Anti-CD47 treatment stimulates phagocytosis of glioblastoma by M1 and M2 polarized macrophages and promotes M1 polarized macrophages in vivo. PLoS ONE. 2016;11(4):e0153550.CrossRefPubMedPubMedCentral
22.
go back to reference Liu ZB, Hou YF, Zhu J, Hu DL, Jin W, Ou ZL, Di GH, Wu J, Shen ZZ, Shao ZM. Inhibition of EGFR pathway signaling and the metastatic potential of breast cancer cells by PA-MSHA mediated by type 1 fimbriae via a mannose-dependent manner. Oncogene. 2010;29(20):2996–3009.CrossRefPubMed Liu ZB, Hou YF, Zhu J, Hu DL, Jin W, Ou ZL, Di GH, Wu J, Shen ZZ, Shao ZM. Inhibition of EGFR pathway signaling and the metastatic potential of breast cancer cells by PA-MSHA mediated by type 1 fimbriae via a mannose-dependent manner. Oncogene. 2010;29(20):2996–3009.CrossRefPubMed
23.
go back to reference Li J, Qu W, Cheng Y, Sun Y, Jiang Y, Zou T, Wang Z, Xu Y, Zhao H. The inhibitory effect of intravesical fisetin against bladder cancer by induction of p53 and down-regulation of NF-kappa B pathways in a rat bladder carcinogenesis model. Basic Clin Pharmacol Toxicol. 2014;115(4):321–9.CrossRefPubMed Li J, Qu W, Cheng Y, Sun Y, Jiang Y, Zou T, Wang Z, Xu Y, Zhao H. The inhibitory effect of intravesical fisetin against bladder cancer by induction of p53 and down-regulation of NF-kappa B pathways in a rat bladder carcinogenesis model. Basic Clin Pharmacol Toxicol. 2014;115(4):321–9.CrossRefPubMed
24.
go back to reference Li J, Wu M, Qu W, Cheng Y, Yu Y, Zou T, Jiang Y, Zhao H. Preventive efects of isetin on bladder cancer in rats and its mechanisms. J Modern Oncol. 2014;22(07):1514–9. Li J, Wu M, Qu W, Cheng Y, Yu Y, Zou T, Jiang Y, Zhao H. Preventive efects of isetin on bladder cancer in rats and its mechanisms. J Modern Oncol. 2014;22(07):1514–9.
25.
go back to reference Tang W, He Y, Zhou S, Ma Y, Liu G. A novel Bifidobacterium infantis-mediated TK/GCV suicide gene therapy system exhibits antitumor activity in a rat model of bladder cancer. J Exp Clin Cancer Res. 2009;28(1):1–7.CrossRef Tang W, He Y, Zhou S, Ma Y, Liu G. A novel Bifidobacterium infantis-mediated TK/GCV suicide gene therapy system exhibits antitumor activity in a rat model of bladder cancer. J Exp Clin Cancer Res. 2009;28(1):1–7.CrossRef
26.
go back to reference Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-∆∆C(T)) method. Methods. 2001;25(4):402–8.CrossRefPubMed Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-∆∆C(T)) method. Methods. 2001;25(4):402–8.CrossRefPubMed
27.
go back to reference Xu WH, Liu ZB, Hou YF, Hong Q, Hu DL, Shao ZM. Inhibition of autophagy enhances the cytotoxic effect of PA-MSHA in breast cancer. BMC Cancer. 2014;14(1):1–9.CrossRefPubMedPubMedCentral Xu WH, Liu ZB, Hou YF, Hong Q, Hu DL, Shao ZM. Inhibition of autophagy enhances the cytotoxic effect of PA-MSHA in breast cancer. BMC Cancer. 2014;14(1):1–9.CrossRefPubMedPubMedCentral
28.
go back to reference Zhu YP, Bian XJ, Ye DW, Yao XD, Zhang SL, Dai B, Shen YJ. Pseudomonas aeruginosa-mannose-sensitive hemagglutinin inhibits proliferation and induces apoptosis in a caspase-dependent manner in human bladder cancer cell lines. Oncol Lett. 2013;5(4):1357–62.PubMedPubMedCentral Zhu YP, Bian XJ, Ye DW, Yao XD, Zhang SL, Dai B, Shen YJ. Pseudomonas aeruginosa-mannose-sensitive hemagglutinin inhibits proliferation and induces apoptosis in a caspase-dependent manner in human bladder cancer cell lines. Oncol Lett. 2013;5(4):1357–62.PubMedPubMedCentral
30.
go back to reference Richards JO, Karki S, Lazar GA, Chen H, Wei D, Desjarlais JR. Optimization of antibody binding to FcγRIIa enhances macrophage phagocytosis of tumor cells. Mol Cancer Ther. 2008;7(8):2517–27.CrossRefPubMed Richards JO, Karki S, Lazar GA, Chen H, Wei D, Desjarlais JR. Optimization of antibody binding to FcγRIIa enhances macrophage phagocytosis of tumor cells. Mol Cancer Ther. 2008;7(8):2517–27.CrossRefPubMed
31.
go back to reference Van Ginderachter JA, Movahedi K, Ghassabeh GH, Meerschaut S, Beschin A, Raes G, De Baetselier P. Classical and alternative activation of mononuclear phagocytes: picking the best of both worlds for tumor promotion. Immunobiology. 2006;211(6–8):487–501.CrossRefPubMed Van Ginderachter JA, Movahedi K, Ghassabeh GH, Meerschaut S, Beschin A, Raes G, De Baetselier P. Classical and alternative activation of mononuclear phagocytes: picking the best of both worlds for tumor promotion. Immunobiology. 2006;211(6–8):487–501.CrossRefPubMed
32.
go back to reference Barresi V, Branca G, Ieni A, Rigoli L, Tuccari G, Caruso RA. Phagocytosis (cannibalism) of apoptotic neutrophils by tumor cells in gastric micropapillary carcinomas. World J Gastroenterol. 2015;21(18):5548–54.CrossRefPubMedPubMedCentral Barresi V, Branca G, Ieni A, Rigoli L, Tuccari G, Caruso RA. Phagocytosis (cannibalism) of apoptotic neutrophils by tumor cells in gastric micropapillary carcinomas. World J Gastroenterol. 2015;21(18):5548–54.CrossRefPubMedPubMedCentral
33.
go back to reference Biswas SK, Lewis CE. NF-κB as a central regulator of macrophage function in tumors. J Leukocyte Biol. 2010;88(5):877–84.CrossRefPubMed Biswas SK, Lewis CE. NF-κB as a central regulator of macrophage function in tumors. J Leukocyte Biol. 2010;88(5):877–84.CrossRefPubMed
34.
go back to reference Mancino A, Lawrence T. Nuclear factor-kappaB and tumor-associated macrophages. Clin Cancer Res. 2010;16(3):784–9.CrossRefPubMed Mancino A, Lawrence T. Nuclear factor-kappaB and tumor-associated macrophages. Clin Cancer Res. 2010;16(3):784–9.CrossRefPubMed
Metadata
Title
PA-MSHA induces apoptosis and suppresses metastasis by tumor associated macrophages in bladder cancer cells
Authors
Jianjun Liu
Xiaoyu Duan
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2017
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-017-0445-3

Other articles of this Issue 1/2017

Cancer Cell International 1/2017 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine