Applications of Human Gastric Cancers Cell Lines (NUGC-4, MKN-45)

Gastric cancer is the 5th-leading type of cancer and 3rd-leading cause of death from cancer. It causes hundreds of thousands of deaths every year[1]. As one of the common types of cancer, gastric cancer is a hot spot in clinical medicine and physiopathology. The pathological mechanisms and treatment methods of gastric cancer are the research focus of scholars.

Gastric Cancer

Gastric cancer, also known as stomach cancer, is cancer that occurs and develops from the lining of the stomach. Most gastric cancer cases are carcinomas such as gastric adenocarcinomas, and lymphomas and mesenchymal tumors may also develop in the stomach (Figure1)[1].Scirrhous gastric cancer (SGC) is a subtype of gastric adenocarcinomas with strong biological aggressiveness. And it accounts for about 10% of all gastric cancer[2]. SGC is easily invading and crossing the stomach wall and attaches to the peritoneum to form peritoneal metastasis[3]. Besides, mucosa-associated lymphoid tissue (MALT) lymphoma is more worthy of attention in gastric lymphomas. And MALT is usually caused by Helicobacter infection[4].

Figure1. Classification of gastric cancer and its incidence distribution[1].

 

Besides Helicobacter infection, cigarettes[5], dietary factors (such as pickled vegetables)[6], diabetes[7], and families[8] are also the causes of gastric cancer. The diagnosis methods of gastric cancer mainly include gastroscopic exam, upper GI series, computed tomography, and histopathological biopsy[9]. The treatment of gastric cancer is a problem in the field of clinical medicine, and it is difficult to cure and poor prognosis unless caught early. Common treatments of gastric cancer include surgery, chemotherapy, radiation, and targeted therapy is the future development direction[10].

Figure2. Endoscopic images of the stomach cancer in early stage[1].

 

Introduction and culture protocol of Human Gastric Cancers Cell Lines

Gastric cancer immortalized cell line is a common tool in the research of gastric cancer physiology, pathology, and clinical medicine. And human-derived cell lines are the most widely used. There are many commonly used gastric cancer cell lines, such as MKN-45, GCR1, mkn7 for not scirrhous and NUGC4, GCIY, OCUM-1 for scirrhous cancer[2]. Gastric cancer cell lines can be used for in vitro functional experiments and cell-derived xenograft (CDX). CDX is widely used in the research of gastric cancer. And CDX can be used to establish a metastasis model based on gastric cancer cells[11].

 

NUGC4 and MKN45 are commonly used human gastric cancer cell lines. Cell line MKN-45 is poorly differentiated adenocarcinoma cells isolated from a 62 years-old Asian female patient, and the production of carcinoembryonic antigen (CEA) of MKN-45 is higher than the normal level[11]. Cell line NUGC4 is signet ring cell carcinoma cells isolated from a 35 years-old Asian female patient with human epidermal growth factor receptor 2 positive (HER2+). These two cell lines are both spherical and adherent culture cell lines. The culture protocol of NUGC-4 and MKN-45 is not much different from other immortalized cell lines cultured on the wall, and they are all cultures in RMPI-1640 with 10% FBS[11].

 

Application of Human Gastric Cancer Cell Lines NUGC-4 and MKN-45

Application of NUGC-4 in the research of gastric cancer

As a human gastric cancer immortalized cell line, NUGC-4 can be used as an in vitro model for gastric cancer research or an implanter of the CDX model. And in some high-impact publications, the above two applications will appear at the same time.

 

Yasumoto, et al. use NU-GC-4 to explore the mechanism of peritoneal cancer induced by gastric cancer[12, 13]. They identify Chemokine signal axis CXCR4/CXCL12 is involved in the mechanism of gastric cancer in the abdominal cavity, and NUGC4 shows a high expression level of CXCR4 and EGFR. Combined with the results of the presence of amphiregulin and HB-EGF detected in malignant ascites in patients with gastric cancer, NUGC4 shows enhanced proliferation, migration, and functional CXCR4 expression levels after the treatment of amphiregulin and HB-EGF. And then, they identify TNFα-converting enzyme (TACE, express in NUGC-4) as a key regulator of the amphiregulin secretion in NUGC-4 cells. Besides, they establish a CDX mouse peritoneal cancer ascites model based on NUGC4 and verify the inhibition of EGFR signal by cetuximab can inhibit the development of ascites induced by NUGC4 implant. All in all, they used the NUGC4-based in vitro model and CDX mouse model to analyze the role of EGFR/amphiregulin/HB-EGF and CXCR4/CXCL12 axis in gastric and peritoneal cancer.

 

Application of MKN-45 in the research of gastric cancer

Similar to NUGC4, MKN-45 can be used as an in vitro model of gastric cancer or a CDX model implanter.

 

Li, et al. used MKN45 combined with clinical samples and data to discover the potential mechanism of gastric cancer cell migration and invasion[14]. They use human gastric cancer cell line MKN 45 co-culture with tumor-associated neutrophils (TANs) from patients with gastric cancer. They found that TAN can produce IL-17a to induce the epithelial to mesenchymal transition (EMT) of MKN45 through JAK2/STAT3 This results in an increase in gastric cancer cell migration and invasion.

 

Chen, et al. use mkn45 to identify another mechanism of the invasion and metastasis of gastric cancer[15]. They found that Contactin-1 (CNTN-1) can induce the invasion and metastasis of MKN 45. And then, they use CNTN-1 shRNA treat mkn45 to perform a second verification of the above conclusions. Besides, they also proved the above conclusions in vivo through nude mouse tumor formation experiments.

Conclusion

As valuable tools, human gastric cancer immortalized cell lines are widely used in the research of gastric cancer. It is very important for the researchers to choose more suitable cell lines for the current work among a variety of gastric cancer cell lines. Choosing the right cell line can help researchers get their jobs done.

 

Where to get Human Gastric Cancer Cell Lines

AcceGen are committed to offering the most complete cell lines with the most favorable price. AcceGen provides the most authentic human tumor cell lines for any specific research needs. Besides NUGC-4 and MKN-45, many other Human Gastric Cancer Cell Lines are also available in AcceGen.

 

It is our pleasure to help relative researches to move forward. All the products of AcceGen are strictly comply with international standards. For more detailed information, please visit our product portfolio or contact inquiry@accegen.com.

 

Reference

  1. wikipedia: gastric cancer. https://enwikipediaorg/wiki/Stomach_cancer.
  2. Zhao L, Yasumoto K, Kawashima A, Nakagawa T, Takeuchi S, Yamada T, Matsumoto K, Yonekura K, Yoshie O, Yano S: Paracrine activation of MET promotes peritoneal carcinomatosis in scirrhous gastric cancer. Cancer Sci 2013, 104:1640-1646.
  3. Yashiro M, Matsuoka T, Ohira M: The significance of scirrhous gastric cancer cell lines: the molecular characterization using cell lines and mouse models. Hum Cell 2018, 31:271-281.
  4. Pereira MI, Medeiros JA: Role of Helicobacter pylori in gastric mucosa-associated lymphoid tissue lymphomas. World J Gastroenterol 2014, 20:684-698.
  5. Nomura A, Grove JS, Stemmermann GN, Severson RK: Cigarette smoking and stomach cancer. Cancer Res 1990, 50:7084.
  6. González CA, Sala N, Rokkas T: Gastric cancer: epidemiologic aspects. Helicobacter 2013, 18 Suppl 1:34-38.
  7. Tseng CH, Tseng FH: Diabetes and gastric cancer: the potential links. World J Gastroenterol 2014, 20:1701-1711.
  8. Oliveira C, Pinheiro H, Figueiredo J, Seruca R, Carneiro F: Familial gastric cancer: genetic susceptibility, pathology, and implications for management. Lancet Oncol 2015, 16:e60-70.
  9. Thrumurthy SG, Chaudry MA, Hochhauser D, Mughal M: The diagnosis and management of gastric cancer. Bmj 2013, 347:f6367.
  10. Orditura M, Galizia G, Sforza V, Gambardella V, Fabozzi A, Laterza MM, Andreozzi F, Ventriglia J, Savastano B, Mabilia A, et al: Treatment of gastric cancer. World J Gastroenterol 2014, 20:1635-1649.
  11. Miwa T, Kanda M, Umeda S, Tanaka H, Shimizu D, Tanaka C, Kobayashi D, Hayashi M, Yamada S, Nakayama G, et al: Establishment of Peritoneal and Hepatic Metastasis Mouse Xenograft Models Using Gastric Cancer Cell Lines. In Vivo 2019, 33:1785-1792.
  12. Yasumoto K, Yamada T, Kawashima A, Wang W, Li Q, Donev IS, Tacheuchi S, Mouri H, Yamashita K, Ohtsubo K, Yano S: The EGFR ligands amphiregulin and heparin-binding egf-like growth factor promote peritoneal carcinomatosis in CXCR4-expressing gastric cancer. Clin Cancer Res 2011, 17:3619-3630.
  13. Yasumoto K, Koizumi K, Kawashima A, Saitoh Y, Arita Y, Shinohara K, Minami T, Nakayama T, Sakurai H, Takahashi Y, et al: Role of the CXCL12/CXCR4 axis in peritoneal carcinomatosis of gastric cancer. Cancer Res 2006, 66:2181-2187.
  14. Li S, Cong X, Gao H, Lan X, Li Z, Wang W, Song S, Wang Y, Li C, Zhang H, et al: Tumor-associated neutrophils induce EMT by IL-17a to promote migration and invasion in gastric cancer cells. J Exp Clin Cancer Res 2019, 38:6.
  15. Chen DH, Yu JW, Wu JG, Wang SL, Jiang BJ: Significances of contactin-1 expression in human gastric cancer and knockdown of contactin-1 expression inhibits invasion and metastasis of MKN45 gastric cancer cells. J Cancer Res Clin Oncol 2015, 141:2109-2120.

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