Abstract
Cancer testis antigens SEMG1 and SEMG2 (semenogelins 1 and 2) are the main proteins of human seminal fluid and are also expressed in malignant neoplasms of various origins. The biological role of semenogelins in the reproductive process is well understood, but almost nothing is known about their functions in tumor cells. In the present study, we used Mia-Paca2 cell line with overexpression of SEMG1 and SEMG2a as a cell model of human pancreatic cancer. Mia-Paca2 cells transduced with the corresponding vector served as control. Using flow cytometry and dihydroethidium (DHE) fluorescent agent detecting predominantly superoxide anion, we have shown that overexpression of SEMG1 and SEMG2 increases the ROS level. In addition, both semenogelins increased the susceptibility of tumor cells to the widely used chemotherapeutic genotoxic drugs doxorubicin and cisplatin. These findings showed that oncosuppressive properties are possessed by SEMG1 and SEMG2 in the cell model of pancreatic cancer.
Similar content being viewed by others
REFERENCES
Baffy, G., Derdak, Z., and Robson, S.C., Mitochondrial recoupling: a novel therapeutic strategy for cancer?, Br. J. Cancer, 2011, vol. 105, pp. 469–474.
Bourgeon, F., Evrard, B., Brillard-Bourdet, M., Colleu, D., Jégou, B., and Pineau, C., Involvement of semenogelin-derived peptides in the antibacterial activity of human seminal plasma, Biol. Reprod., 2004, vol. 70, pp. 768–774.
Canacci, A.M., Izumi, K., Zheng, Y., Gordetsky, J., Yao, J.L., and Miyamoto, H., Expression of semenogelins I and II and its prognostic significance in human prostate cancer, Prostate, 2011, vol. 71, pp. 1108–1114.
Deavall, D.G., Martin, E.A., Horner, J.M., and Roberts, R., Drug-induced oxidative stress and toxicity, J. Toxicol., 2012, vol. 2012, p. 645460. https://doi.org/10.1155/2012/645460
Figueiredo, D.L., Mamede, R.C., Proto-Siqueira, R., Neder, L., Silva, W.A., and Zago, M.A., Expression of cancer testis antigens in head and neck squamous cell carcinomas, Head Neck, 2006, vol. 28, pp. 614–619.
Freitas, M.R.P., Malheiros, S.M.F., Stavale, J.N., Biassi, T.P., Zamuner, F.T., de, Souza, Begnami, M.D.F., and Vettore, A.L., Expression of cancer/testis antigens is correlated with improved survival in glioblastoma, Oncotarget, 2013, vol. 4, pp. 636–646.
Gjerstorff, M.F., Andersen, M.H., and Ditzel, H.J., Oncogenic cancer/testis antigens: prime candidates for immunotherapy, Oncotarget, 2015, vol. 6, pp. 15772–15787.
Jonsson, M., Lundwall, Å., and Malm, J., The semenogelins: proteins with functions beyond reproduction?, Cell Mol. Life Sci., 2006, vol. 63, pp. 2886–2888.
Kizenko, A. I., Fedorova, O. A., Daks, A. A., Petukhov, A. V., Barlev, N. A., and Shuvalov, O. Yu., Cancer-testicular antigens—semenogelines 1 and 2: functions in the reproductive process and oncogenesis, Tsitologiia, 2018, vol. 60, no. 9, pp. 679–685.
Lamirande, E., and Lamothe, G., Levels of semenogelin in human spermatozoa decrease during capacitation: involvement of reactive oxygen species and zinc, Hum. Reprod., 2010, vol. 25, pp. 1619–1630.
Lamirande, E., Yoshida, K., Yoshiike, M., Iwamoto, T., and Gagnon, C., Semenogelin, the main protein of semen coagulum, inhibits human sperm capacitation by interfering with the superoxide anion generated during this process, J. Androl., 2001, vol. 22, pp. 672–679.
Murphy, M.P., How mitochondria produce reactive oxygen species, Biochem. J., 2009, vol. 417, pp. 1–13.
Prasad, M.L., Jungbluth, A.A., Patel, S.G., Iversen, K., Hoshaw-Woodard, S., and Busam, K.J., Expression and significance of cancer testis antigens in primary mucosal melanoma of the head and neck, Head Neck, 2004, vol. 26, pp. 1053–1057.
Rodrigues, S.M., Schafe, G.E., and LeDoux, J.E., Intra-amygdala blockade of the NR2B subunit of the NMDA receptor disrupts the acquisition but not the expression of fear conditioning, J. Neurosci., 2001, vol. 21, pp. 6889–6896.
Shuvalov, O., Kizenko, A., Shakirova, A., Fedorova, O., Petukhov, A., Aksenov, N., Vasileva, E., Daks, A., and Barlev, N., Nutlin sensitizes lung carcinoma cells to interferon-alpha treatment in MDM2-dependent but p53-independent manner, Biochem. Biophys. Res. Commun., 2018, vol. 495, pp. 1233–1239.
Silva, V.L., Fonseca, A.F., Fonseca, M., Silva, T.E., Coelho, A.C., Kroll, J.E., and Souza, S.J., Genome-wide identification of cancer/testis genes and their association with prognosis in a pan-cancer analysis, Oncotarget, 2017, vol. 8, pp. 92966–92977.
Velazquez, E.F., Jungbluth, A.A., Yancovitz, M., Gnjatic, S., Adams, S., O’Neill, D., and Pavlick, A., Expression of the cancer/testis antigen NY-ESO-1 in primary and metastatic malignant melanoma (MM)—correlation with prognostic factors, Cancer Immun. Arch., 2007, vol. 7, pp. 1–7.
Zhang, Y., Wang, Z., Liu, H., Giles, F.J., and Lim, S.H., Pattern of gene expression and immune responses to semenogelin 1 in chronic hematologic malignancies, J. Immunother., 2003, vol. 26, pp. 461–467.
Zhang, S., Fang, J., Zhang, X., Qin, C., Su, S., Deng, and Wang, Z., Seminal plasma protein in renal cell carcinoma: expression of semenogelin i is a predictor for cancer progression and prognosis, Tumor Biol., 2014, vol. 35, pp. 9095–9100.
Funding
This study was supported by the Russian Science Foundation, project no. 17-75-10205.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.
Additional information
Translated by I. Fridlyanskaya
Abbreviations: ROS—reactive oxygen species, CTA—cancer testis antigens, 2DHE—dihydroethidium, SEMG1—semenogelin 1, SEMG2—semenogelin 2.
Rights and permissions
About this article
Cite this article
Shuvalov, O.Y., Kizenko, A.I., Petukhov, A.V. et al. Oncosupressor Properties of SEMG1 and SEMG2 Cancer-Testicular Antigens in the Cell Model of Human Pancreatic Carcinoma Mia-Paca2. Cell Tiss. Biol. 14, 124–128 (2020). https://doi.org/10.1134/S1990519X20020108
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1990519X20020108