Volume 25, Issue 5 (9-2021)                   ibj 2021, 25(5): 310-322 | Back to browse issues page

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Balouchi-Anaraki S, Ahmadvand S, Safaei A, Ghaderi A. 4H12, a Murine Monoclonal Antibody Directed against Myosin Heavy Chain-9 Expressed on Acinar Cell Carcinoma of Pancreas with Potential Therapeutic Application. ibj. 2021; 25 (5) :310-322
URL: http://ibj.pasteur.ac.ir/article-1-3276-en.html
Background: Pancreatic acinar cell carcinoma (PACC) is a rare type of pancreatic exocrine neoplasm that is frequently diagnosed at late stages with a high rate of metastasis. Identification of new biomarkers for PACC can improve our knowledge of its biology, early detection, or targeted therapy. In this study, hybridoma technology was used to generate mAbs against Faraz-ICR, a pancreatic acinar cell carcinoma cell line. Methods: Cell ELISA and flow cytometry were used for screening, and the 4H12 hybridoma clone was selected for further analysis. The 4H12 mAb was specific for myosin heavy chain-9 (MYH9) as determined by Immunoprecipitation, Western blot, and mass spectrometry. Results: This antibody reacted variably with other cancer cells, in comparison to Faraz-ICR cell. Besides, by immunohistochemical staining, the acinar cell tumor, which was the source of Faraz-ICR, showed high MYH9 expression. Among 21 pancreatic ductal adenocarcinoma cases, nine (42.8%) expressed MYH9 with low intensity, while 10 (47.8%) and 2 (9.5%) cases expressed MYH9 with moderate to strong intensities, respectively. The 4H12 mAb inhibited the proliferation of Faraz-ICR cells in a dose-dependent manner from 0.75 to 12.5 μg/ml concentrations (p < 0.0001 and p < 0.002). IC50 values were achieved at 12.09 ± 4.19 µg/ml and 7.74 ± 4.28 µg/ml after 24- and 48-h treatment, respectively. Conclusion: Our data suggest that the 4H12 mAb can serve as a tool for investigating the role of MYH9 pancreatic cancer biology and prognosis.
Type of Study: Full Length | Subject: Cancer Biology

1. Rawla P, Sunkara T, Gaduputi V. Epidemiology of pancreatic cancer: Global trends, etiology and risk factors. World journal of oncology 2019; 10(1): 10-27. [DOI:10.14740/wjon1166]
2. Klimstra DS. Nonductal neoplasms of the pancreas. Modern pathology 2007; 20: S94-S112. [DOI:10.1038/modpathol.3800686]
3. Chaudhary P. Acinar Cell Carcinoma of the Pancreas: A literature review and update. Indian journal of surgery 2015; 77(3): 226-231. [DOI:10.1007/s12262-014-1049-y]
4. Glazer ES, Neill KG, Frakes JM, Coppola D, Hodul PJ, Hoffe SE, Pimiento JM, Springett GM, Malafa MP. Systematic review and case series report of acinar cell carcinoma of the pancreas. Cancer control 2016; 23(4): 446-454. [DOI:10.1177/107327481602300417]
5. Butturini G, Pisano M, Scarpa A, D'Onofrio M, Auriemma A, Bassi C. Aggressive approach to acinar cell carcinoma of the pancreas: a single-institution experience and a literature review. Langenbeck's archives of surgery 2011; 396(3): 363-369. [DOI:10.1007/s00423-010-0706-2]
6. Klimstra DS, Heffess CS, Oertel JE, Rosai J. Acinar cell carcinoma of the pancreas. A clinicopathologic study of 28 cases. The American journal of surgical pathology 1992; 16(9): 815-837. [DOI:10.1097/00000478-199209000-00001]
7. Di Marco M, Carloni R, De Lorenzo S, Grassi E, Palloni A, Formica F, Brocchi S, Filippini DM, Golfieri R, Brandi G. Long-term survival of two patients with recurrent pancreatic acinar cell carcinoma treated with radiofrequency ablation: A case report. World journal of clinical cases 2020; 8(7): 1241-1250. [DOI:10.12998/wjcc.v8.i7.1241]
8. Hartwig W, Denneberg M, Bergmann F, Hackert T, Hinz U, Strobel O, Büchler MW, Werner J. Acinar cell carcinoma of the pancreas: is resection justified even in limited metastatic disease? American journal of surgery 2011; 202(1): 23-27. [DOI:10.1016/j.amjsurg.2010.06.004]
9. Chaudhary P, Ranjan G, Chaudhary A, Tiwari A, Arora M. Acinar cell carcinoma: A rare pancreatic malignancy. Clinics and practice 2013; 3: e18. [DOI:10.4081/cp.2013.e18]
10. Burke HB. Predicting clinical outcomes using molecular biomarkers. Biomarker in cancer 2016; 8: 89-99. [DOI:10.4137/BIC.S33380]
11. El Bairi K, Atanasov AG, Amrani M, Afqir S. The arrival of predictive biomarkers for monitoring therapy response to natural compounds in cancer drug discovery. Biomedicine and pharmacotherapy 2019; 109: 2492-2498. [DOI:10.1016/j.biopha.2018.11.097]
12. Tainsky MA. Genomic and proteomic biomarkers for cancer: a multitude of opportunities. Biochimica et biophysica acta 2009; 1796(2): 176-193. [DOI:10.1016/j.bbcan.2009.04.004]
13. Hudler P, Kocevar N, Komel R. Proteomic approaches in biomarker discovery: New perspectives in cancer diagnostics. The scientific world journal 2014; 2014: 260348. [DOI:10.1155/2014/260348]
14. Tanase C, Albulescu R, Neagu M. Proteomic approaches for biomarker panels in cancer. Journal of immunoassay and immunochemistry 2016; 37(1): 1-15. [DOI:10.1080/15321819.2015.1116009]
15. Zhang A, Sun H, Yan G, Wang P, Wang X. Metabolomics for biomarker Discovery: Moving to the Clinic. Biomed research international 2015; 2015: 354671. [DOI:10.1155/2015/354671]
16. Zhang X, Soori G, Dobleman T. The application of monoclonal antibodies in cancer diagnosis. Expert review of molecular diagnostics 2013; 14 (1): 97-106. [DOI:10.1586/14737159.2014.866039]
17. Loo DT, Mather JP. Antibody-based identification of cell surface antigens: targets for cancer therapy. Current opinion in pharmacology 2008; 8(5): 627-631. [DOI:10.1016/j.coph.2008.08.011]
18. Ghaderi F, Ahmadvand S, Ramezani A, Montazer M, Ghaderi A. Production and characterization of monoclonal antibody against a triple negative breast cancer cell line. Biochemical and biophysical research communications 2018; 505(1): 181-186. [DOI:10.1016/j.bbrc.2018.09.087]
19. Schrama D, Reisfeld RA, Becker JC. Antibody targeted drugs as cancer therapeutics. Nature reviews drug discovery 2006; 5(2): 147-159. [DOI:10.1038/nrd1957]
20. Dela Cruz JS, Morrison SL, Penichet ML. Insights into the mechanism of anti-tumor immunity in mice vaccinated with the human HER2/neu extracellular domain plus anti-HER2/neu IgG3-(IL-2) or anti-HER2/neu IgG3-(GM-CSF) fusion protein. Vaccine 2005; 23(39): 4793-4803. [DOI:10.1016/j.vaccine.2005.04.041]
21. Alarfaj NA, El-Tohamy MF, Oraby HF. CA 19-9 pancreatic tumor marker fluorescence immunosensing detection via immobilized carbon quantum dots conjugated gold nanocomposite. International journal molecular sciences 2018; 19(4): 1162 [DOI:10.3390/ijms19041162]
22. Zhang X, Shi S, Zhang B, Ni Q, Yu X, Xu J. Circulating biomarkers for early diagnosis of pancreatic cancer: facts and hopes. American journal of cancer research 2018; 8(3): 332-353
23. Hasan S, Jacob R, Manne U, Paluri R. Advances in pancreatic cancer biomarkers. Oncology reviews 2019; 13(1): 410-410. [DOI:10.4081/oncol.2019.410]
24. Stauffer JA, Asbun HJ. Rare tumors and lesions of the pancreas. The surgical clinics of North America 2018; 98(1): 169-188. [DOI:10.1016/j.suc.2017.09.013]
25. Rezaei M, Hosseini A, Nikeghbalian S, Ghaderi A. Establishment and characterization of a new human acinar cell carcinoma cell line, Faraz-ICR, from pancreas. Pancreatology 2017; 17: 303-309. [DOI:10.1016/j.pan.2017.02.003]
26. Mehdipour F, Razmkhah M, Rezaeifard S, Bagheri M, Talei AR, Khalatbari B, Ghaderi A. Mesenchymal stem cells induced anti-inflammatory features in B cells from breast tumor draining lymph nodes. Cell biology international 2018; 42(12): 1658-1669. [DOI:10.1002/cbin.11062]
27. Kohl TO, Ascoli CA. Direct and indirect cell-based enzyme-linked immunosorbent assay. Cold spring harbor protocols 2017; 2017(5): doi: 10.1101. [DOI:10.1101/pdb.prot093732]
28. Ramezani A, Mahmoudi Maymand E, Yazdanpanah-Samani M, Hosseini A, Toghraie FS, Ghaderi A. Improving pertuzumab production by gene optimization and proper signal peptide selection. Protein expression and purification 2017; 135: 24-32. [DOI:10.1016/j.pep.2017.04.013]
29. Bulut H, Bolat Y. Production and characterization of monoclonal Anti-Ovalbumin antibodies. Turkish journal of medical science 2000; 30: 411-416.
30. Ahmadvand S, Faghih Z, Montazer M, Safaei A, Mokhtari M, Jafari P, Talei AR, Tahmasebi S, Ghaderi A. Importance of CD45RO+ tumor-infiltrating lymphocytes in post-operative survival of breast cancer patients. Molecoolar and cellular oncology 2019; 42(3): 343-356. [DOI:10.1007/s13402-019-00430-6]
31. Patel S, Gheewala N, Suthar A, Shah A, Patel S. In-vitro cytotoxicity activity of Solanum Nigrum extract against Hela cell line and Vero cell line. International journal of pharmacy and pharmaceutical sciences 2009; 1(suppl 1): Nov-Dec.
32. Tian L, Lv XF, Dong J, Zhou J, Zhang Y, Xi SY, Zhang R, Xie CM. Clinical features and CT/MRI findings of pancreatic acinar cell carcinoma. International journal of clinical and experimental medicine 2015; 8(9): 14846-14854.
33. Fontenot J, Spieler B, Hudson C, Boulmay B. Pancreatic acinar cell carcinoma--literature review and case report of a 56-year-old man presenting with abdominal pain. Radiology case reports 2019; 15: 39-43. [DOI:10.1016/j.radcr.2019.10.009]
34. Vicente-Manzanares M, Ma X, Adelstein RS, Horwitz AR. Non-muscle myosin II takes centre stage in cell adhesion and migration. Nature reviews molecular cell biology 2009; 10(11): 778-790. [DOI:10.1038/nrm2786]
35. Fernandez-Prado R, Carriazo-Julio SM, Torra R, Ortiz A, Perez-Gomez MV. MYH9-related disease: it does exist, may be more frequent than you think and requires specific therapy. Clinical kidney journal 2019; 12(4): 488-493. [DOI:10.1093/ckj/sfz103]
36. Wang Y, Liu S, Zhang Y, Yang J. Myosin heavy chain 9: oncogene or tumor suppressor gene? Medical science monitor 2019; 25: 888-892 6. [DOI:10.12659/MSM.912320]
37. Schramek D, Sendoel A, Segal JP, Beronja S, Heller E, Oristian D, Reva B, Fuchs E. Direct in vivo RNAi screen unveils myosin IIa as a tumor suppressor of squamous cell carcinomas. Science 2014; 343(6168): 309-313. [DOI:10.1126/science.1248627]
38. Zhou P, Li Y, Li B, Zhang M, Liu Y, Yao Y, Li D. NMIIA promotes tumor growth and metastasis by activating the Wnt/β-catenin signaling pathway and EMT in pancreatic cancer. Oncogene 2019; 38(27): 5500-5515. [DOI:10.1038/s41388-019-0806-6]
39. Cheng L, Tao X, Qin Y, Wang J, Xu J, Ci H, Wu Q, Zheng D, Wang Q, Cheng Z, Wu S, Tao Y. Aberrant expression of MYH9 and E-cadherin in esophageal squamous cell carcinoma and their relationship to vasculogenic mimicry. International journal of clinical and experimental of pathology 2019; 12(6): 2205-2214.
40. Maeda J, Hirano T, Ogiwara A, Akimoto S, Kawakami T, Fukui Y, Oka T, Gong Y, Guo R, Inada H, Nawa K, Kojika M, Suga Y, Ohira T, Mukai K, Kato H. Proteomic analysis of stage I primary lung adenocarcinoma aimed at individualisation of postoperative therapy. British journal of cancer 2008; 98(3): 596-603. [DOI:10.1038/sj.bjc.6604197]
41. Yu M, Wang J, Zhu Z, Hu C, Ma Q, Li X, Yin X, Huang J, Zhang T, Ma Z, Zhou Y, Li C, Chen F, Chen J, Wang Y, Pan H, Wang D, Jin J. Prognostic impact of MYH9 expression on patients with acute myeloid leukemia. Oncotarget 2017; 8(1): 156-163. [DOI:10.18632/oncotarget.10613]
42. Watanabe TK, Kuczmarski ER, Reddy JK. Myosin from pancreatic acinar carcinoma cells. Isolation, characterization and demonstration of heavy- and light-chain phosphorylation. The Biochemical journal 1987; 247(3): 513-518. [DOI:10.1042/bj2470513]
43. Liu Y, Li R, Chen XX, Zhi Y, Deng R, Zhou EM, Qiao S, Zhang G. Nonmuscle myosin heavy chain IIA recognizes sialic acids on sialylated RNA viruses to suppress proinflammatory responses via the DAP12-Syk pathway. AMS journals 2019; 10(3) :e00574-19. [DOI:10.1128/mBio.00574-19]
44. Xiong D, Du Y, Wang HB, Zhao B, Zhang H, Li Y, Hu LJ, Cao JY, Zhong Q, Liu WL, Li MZ, Zhu XF, Tsao S, Hutt-Fletcher L, Song E, Zeng YX, Kieff E, Zeng MS. Nonmuscle myosin heavy chain IIA mediates Epstein-Barr virus infection of nasopharyngeal epithelial cells. Proceedings of the National Academy of Sciences of the United States of America 2015; 112: 11036-11041. [DOI:10.1073/pnas.1513359112]
45. Katono K, Sato Y, Jiang S-X, Kobayashi M, Nagashio R, Ryuge S, Fukuda E, Goshima N, Satoh Y, Saegusa M, Masuda N. Prognostic significance of MYH9 expression in resected non-small cell lung cancer. PLoS one 2015; 10(3): e0121460-e0121460. [DOI:10.1371/journal.pone.0121460]
46. Lin X, Li Am, Li YH, Luo RC, Zou YJ, Liu YY, Liu C, Xie YY, Zuo S, Liu Z, Liu Z, Fang WY. Silencing MYH9 blocks HBx-induced GSK3β ubiquitination and degradation to inhibit tumor stemness in hepatocellular carcinoma. Signal transduction and targeted therapy 2020; 5(1): 13. [DOI:10.1038/s41392-020-0111-4]
47. Wang B, Qi X, Liu J, Zhou R, Lin C, Shangguan J, Zhang Z, Zhao L, Li G. MYH9 promotes growth and metastasis via activation of MAPK/AKT signaling in colorectal cancer. Journal of cancer 2019; 10(4): 874-884. [DOI:10.7150/jca.27635]

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