Pre-clinical results show that PA-MSHA may inhibit progression of bladder cancer

Liz Meszaros, MDLinx | August 28, 2017

Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA)—a gram-negative bacterium—may promote apoptosis in mouse bladder cancer cells by inducing M1 polarization, as well as inhibit proliferation, invasion, and migration of these cells, according to a recent study published in the journal Cancer Cell International.

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Bladder cancer research

Researchers have shown that PA-MSHA promotes apoptosis in mouse bladder cancer cells.

“Bladder cancer, one of the most common form of urologic cancers, is a primary clinical problem worldwide,”1 wrote authors Jianjun Liu and Xiaoyu Duan, Henan Provincial People’s Hospital, Zhengzhou, China. “It is the main cause of death among urinary tumors in China.2 The incidence of bladder cancer has been on the increase in recent years, with approximately 75% to 85% of the diagnosed tumors being non-muscle invasive bladder cancer.3 The patients afflicted with nonmuscle-invasive bladder cancer are susceptible to a high recurrence rate, ranging from 50% to 70%.4,5 Moreover, because of the aggressive nature of this cancer, 10% to 20% of non-muscle-invasive bladder cancer may rapidly progress to muscle-invasive disease.” 5,6

The PA-MSHA strain of P. aeruginosa is comprised of a peritrichous P. aeruginosa strain with MSHA fimbriae, and has been shown to improve immune responses in some types of cancer, infection, trauma, and chronic disease. It has also been widely used as a vaccine in anti-inflammatory, anti-infection, and anti-cancer treatments. With the addition of MSHA, PA-MSHA is cytotoxic, and has been shown to exhibit anticarcinogenic effects as well.

These researchers, therefore, conducted this study to assess the possible inhibitory effects of PA-MSHA on the proliferation of bladder cancer cell lines, as well as to further define the functional mechanisms of PA-MSHA.

Using a rat model of bladder tumor induced by intravesical N-methyl-N nitrosourea, they measured the dynamic growth of tumors via whole-body fluorescent imaging. Using microscopic exam and hematoxylin-eosin staining, Liu and Duan conducted their morphological analysis, and via immunohistochemistry, detected Caspase 3 and E-Ca expression. In addition, they used flow cytometry to separate macrophages, and measured cytokine expression via qRT-PCR and Western blot. Finally, they measured apoptosis ability via annexin V and propidium iodide, and invasion and migration abilities by transwell migration and scratch assays.

Liu and Duan found that PA-MSHA and PA-MSHA plus fisetin inhibited tumor growth and increased the M1/M2 ratio. PA-MSHA suppressed bladder tumor cell invasive abilities, as well as promoted bladder tumor cell apoptosis. It also facilitated M1 cytokine expression, while reducing M2 cytokine expression. Finally, mouse M1 phagocytosis rates were higher when treated with PA-MSHA compared with those of M2 macrophages for bladder cancer lines.

“The results of the current study suggested that PA-MSHA induced M1 polarization and therefore inhibited tumor growth and bladder cell proliferation. This mechanism might be a potential novel strategy for inhibiting bladder carcinoma progression in the mouse,” concluded these authors.

References

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. A Cancer J Clin. 2013;63(1):11–30.
  2. Jemal A, Bray F, Center MM, Ferlay JJ, Ward E, Forman D. Global cancer statistics. Cancer J Clin. 2011;61(2):69–90.
  3. Wirth M, Plattner VE, Gabor F. Strategies to improve drug delivery in bladder cancer therapy. Exp Opin Drug Deliv. 2009;6(6):727–744.
  4. Mansoor M, Ali S, Fasihuddin Q, Baloch MU. Superficial bladder tumours: Recurrence and progression. J Coll Phys Surg Pak. 2011;21(3):157–160.
  5. 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.
  6. Herr HW. High-risk superficial bladder cancer: transurethral resection alone in selected patients with T1 tumor. J Urol. 1997;160(5):1934.

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