Expression of lactate dehydrogenase C in MDA‑MB‑231 cells and its role in tumor invasion and migration

Kong,Lingying; Du,Wei; Cui,Zhaolei; Wang,Li; Yang,Zhi; Zhang,Hongsheng; Lin,Donghong

doi:10.3892/mmr.2016.4963

Expression of lactate dehydrogenase C in MDA‑MB‑231 cells and its role in tumor invasion and migration

Authors:
- Lingying Kong
- Wei Du
- Zhaolei Cui
- Li Wang
- Zhi Yang
- Hongsheng Zhang
- Donghong Lin
View Affiliations

Affiliations: Department of Pathology, Fujian University of Traditional Chinese Medicine Affiliated People's Hospital, Taijiang, Fuzhou, Fujian 350004, P.R. China, Department of Clinical Laboratory, School of Medical Technology and Engineering, Fujian Medical University, Taijiang, Fuzhou, Fujian 350004, P.R. China
Published online on: March 2, 2016 https://doi.org/10.3892/mmr.2016.4963
Pages: 3533-3538

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The cancer/testis antigen (CTA) lactate dehydrogenase C (LDHC) is a unique LDH isoenzyme associated with glucose and adenosine triphosphate production in mammalian germ cells. However, the role of LDHC in cancer has thus far largely remained elusive. The present study described the expression status of LDHC in human MDA‑MB‑231 breast cancer cells as well as its role in tumor invasion and migration. Immunohistochemical analysis revealed endogenous LDHC expression in the cytoplasm and nuclei of MDA‑MB‑231 cells yielded. In addition, in vitro cell invasion and migration assays revealed that when LDHC expression was blocked by its specific inhibitor, cell invasion and migration were compromised in MDA‑MB‑231 cells. Of note, inhibition of LDHC was unable to induce apoptosis in MDA‑MB‑231 cells. The present study provided evidence that the LDHC enzyme acts as a CTA in breast carcinoma and exerts an essential role in tumor invasion and migration.

View Figures

View References

1	Echigoya Y, Sato T, Itou T, Endo H and Sakai T: Molecular characterization and expression pattern of the equine lactate dehydrogenase A and B genes. Gene. 447:40–50. 2009. View Article : Google Scholar : PubMed/NCBI
2	Edmunds RC, van Herwerden L, Smith-Keune C and Jerry DR: Comparative characterization of a temperature responsive gene (lactate dehydrogenase-B, ldh-b) in two congeneric tropical fish, Lates calcarifer and Lates niloticus. Int J Biol Sci. 5:558–569. 2009. View Article : Google Scholar : PubMed/NCBI
3	Dutta RC and Goldberg E: Testis specific lactate dehydrogenase as target for immunoliposomes. Am J Reprod Immunol. 60:26–32. 2008. View Article : Google Scholar : PubMed/NCBI
4	Miao P, Sheng S, Sun X, Liu J and Huang G: Lactate dehydro-genase A in cancer: A promising target for diagnosis and therapy. IUBMB Life. 65:904–910. 2013. View Article : Google Scholar : PubMed/NCBI
5	Granchi C, Paterni I, Rani R and Minutolo F: Small-molecule inhibitors of human LDH5. Future Med Chem. 5:1967–1991. 2013. View Article : Google Scholar : PubMed/NCBI
6	Goldberg E, Eddy EM, Duan C and Odet F: LDHC: The ultimate testis-specific gene. J Androl. 31:86–94. 2010. View Article : Google Scholar :
7	Cui Z, Chen L, Liu Y, Zeng Z and Lan F: Quick histochemical staining method for measuring lactate dehydrogenase C4 activity in human spermatozoa. Acta Histochemica. 117:235–242. 2015. View Article : Google Scholar : PubMed/NCBI
8	Odet F, Duan C, Willis WD, Goulding EH, Kung A, Eddy EM and Goldberg E: Expression of the gene for mouse lactate dehy-drogenase C (Ldhc) is required for male fertility. Biol Reprod. 79:26–34. 2008. View Article : Google Scholar : PubMed/NCBI
9	Odet F, Gabel SA, Williams J, London RE, Goldberg E and Eddy EM: Lactate dehydrogenase C and energy metabolism in mouse sperm. Biol Reprod. 85:556–564. 2011. View Article : Google Scholar : PubMed/NCBI
10	Odet F, Gabel S, London RE, Goldberg E and Eddy EM: Glycolysis and mitochondrial respiration in mouse LDHC-null sperm. Biol Reprod. 88:952013. View Article : Google Scholar : PubMed/NCBI
11	Cordero-Martínez J, Aguirre-Alvarado C, Wong C and Rodríguez-Páez L: Effect of oxamic analogues on functional mice sperm parameters. Syst Biol Reprod Med. 60:189–198. 2014. View Article : Google Scholar : PubMed/NCBI
12	Koslowski M, Türeci O, Bell C, Krause P, Lehr HA, Brunner J, Seitz G, Nestle FO, Huber C and Sahin U: Multiple splice variants of lactate dehydrogenase C selectively expressed in human cancer. Cancer Res. 62:6750–6755. 2002.PubMed/NCBI
13	Bonuccelli G, Tsirigos A, Whitaker-Menezes D, Pavlides S, Pestell RG, Chiavarina B, Frank PG, Flomenberg N, Howell A, Martinez-Outschoorn UE, et al: Ketones and lactate "fuel" tumor growth and metastasis: Evidence that epithelial cancer cells use oxidative mitochondrial metabolism. Cell Cycle. 9:3506–3514. 2010. View Article : Google Scholar : PubMed/NCBI
14	Rodríguez-Páez L, Chena-Taboada MA, Cabrera-Hernández A, Cordero-Martínez J and Wong C: Oxamic acid analogues as LDH-C4-specific competitive inhibitors. J Enzyme Inhib Med Chem. 26:579–586. 2011. View Article : Google Scholar : PubMed/NCBI
15	Zhang H, Kong L, Cui Z, Du W, He Y, Yang Z, Wang L and Chen X: The WWOX gene inhibits the growth of U266 multiple myeloma cells by triggering the intrinsic apoptotic pathway. Int J Mol Med. 34:804–809. 2014.PubMed/NCBI
16	Ma L, Lan F, Zheng Z, Xie F, Wang L, Liu W, Han J, Zheng F, Xie Y and Huang Q: Epidermal growth factor (EGF) and interleukin (IL)-1β synergistically promote ERK1/2-mediated invasive breast ductal cancer cell migration and invasion. Mol Cancer. 11:792012. View Article : Google Scholar
17	Wang N, Wei H, Yin D, Lu Y, Zhang Y, Jiang D, Jiang Y and Zhang S: Cyclin D1b overexpression inhibits cell proliferation and induces cell apoptosis in cervical cancer cells in vitro and in vivo. Int J Clin Exp Pathol. 7:4016–4023. 2014.PubMed/NCBI
18	Lin D, Cui Z, Kong L, Cheng F, Xu J and Lan F: p73 participates in WWOX-mediated apoptosis in leukemia cells. Int J Mol Med. 31:849–854. 2013.PubMed/NCBI
19	De Smet C, Lurquin C, Lethé B, Martelange V and Boon T: DNA methylation is the primary silencing mechanism for a set of germ line- and tumor-specific genes with a CpG-rich promoter. Mol Cell Biol. 19:7327–7335. 1999. View Article : Google Scholar : PubMed/NCBI
20	Miskimins WK, Ahn HJ, Kim JY, Ryu S, Jung YS and Choi JY: Synergistic anti-cancer effect of phenformin and oxamate. PLoS One. 9:e855762014. View Article : Google Scholar : PubMed/NCBI
21	Rizwan A, Serganova I, Khanin R, Karabeber H, Ni X, Thakur S, Zakian KL, Blasberg R and Koutcher JA: Relationships between LDH-A, lactate and metastases in 4T1 breast tumors. Clin Cancer Res. 19:5158–5169. 2013. View Article : Google Scholar : PubMed/NCBI
22	Yang Y, Su D, Zhao L, Zhang D, Xu J, Wan J, Fan S and Chen M: Different effects of LDH-A inhibition by oxamate in non-small cell lung cancer cells. Oncotarget. 5:11886–11896. 2014. View Article : Google Scholar : PubMed/NCBI