IHC characteristics of stem cell markers in PDAC with different degrees of differentiation
DOI:
https://doi.org/10.12775/JEHS.2022.12.06.023Keywords
Pancreas, Ductal adenocarcinoma, Cancer stem cells, EpCAM, CD44Abstract
Introduction. Cancer stem cells (CSCs) play a key role in the development, progression and metastasis of cancer. Cell surface markers, in particular CD44 and EpCAM, are used to identify CSCs. Marker expression patterns depend on the stage of progression and differentiation. Materials and methods. Histopathological and IHC studies of 49 cases of the pancreas ductal adenocarcinoma (PDAC) of G2, G3 degrees of differentiation. Results of IHC reactions with antibodies against CD44 and EpCAM were estimated by photo digital morphometry and were expressed in immunostained cells relative area (%). Results. Adenocarinoma of the pancreas is characterized by a moderate level of expression of cell surface markers CSC - CD44 and EpCAM. The expression level of CD44 in the І gr. - Me = 34.11% (Q1 = 31.03; Q3 = 38.39), in the II gr. - Me = 43.17% (Q1 = 39.83; Q3 = 47.04), significantly higher than in the I gr. (Kruskal-Wallis test p<0.05). The expression level of EpCAM in the I gr. - Ме=26,10% (Q1=20,42; Q3=31,89), in the II gr. - Ме=31,07% (Q1=27,03; Q3=34,00) (p>0,05). In both groups, the relative area of EpCAM was significantly lower than CD44 (Kruskal-Wallis test p<0.05). Correlation analysis (Pearson's ratio) showed a weak negative relationship between markers at G2 (r = -0.17, p>0.05), at G3 - a weak positive (r = + 0.06, p>0.05).
References
Ishiwata, T., Matsuda, Y., Yoshimura, H., Sasaki, N., Ishiwata, S., Ishikawa, N., Takubo, K, Arai, T., Aida, J. (2018). Pancreatic cancer stem cells: features and detection methods. Pathol Oncol Res. 24(4):797-805. https://doi: 10.1007/s12253-018-0420-x.
Jo, J.H., Kim, S.A., Lee, J.H. et al. (2021). GLRX3, a novel cancer stem cell-related secretory biomarker of pancreatic ductal adenocarcinoma. BMC Cancer. 18;21(1):1241. https://doi: 10.1186/s12885-021-08898-y.
Subramaniam, D., Kaushik, G., Dandawate, P., Anant, Sh. (2018). Targeting Cancer Stem Cells for Chemoprevention of Pancreatic Cancer. Curr Med Chem. 25(22):2585-2594. https://doi: 10.2174/0929867324666170127095832.
Ercan, G., Karlitepe, A., Ozpolat, B. (2017). Pancreatic Cancer Stem Cells and Therapeutic Approaches. Anticancer Res. 37(6):2761-2775. https://doi: 10.21873/anticanres.11628.
Gaertner, B., Carrano, A. C, Sander, M. (2019). Human stem cell models: lessons for pancreatic development and disease. Genes Dev. 1;33(21-22):1475-1490. https://doi: 10.1101/gad.331397.119.
Wu Y, Zhang C, Jiang K, Werner J, Bazhin AV and D’Haese JG (2021) The Role of Stellate Cells in Pancreatic Ductal Adenocarcinoma: Targeting Perspectives. Front. Oncol. 10:621937. https://doi: 10.3389/fonc.2020.621937
Zhou, P., Li, B., Liu, F., Zhang, M., Wang, Q., Liu, Y., Yao, Y., Li, D. (2017). The epithelial to mesenchymal transition (EMT) and cancer stem cells: implication for treatment resistance in pancreatic cancer. Mol Cancer. 28;16(1):52. https://doi: 10.1186/s12943-017-0624-9.
Ahmad R Safa (2020). Epithelial-mesenchymal transition: a hallmark in pancreatic cancer stem cell migration, metastasis formation, and drug resistance. J Cancer Metastasis Treat. 6:36. https://doi: 10.20517/2394-4722.2020.55. Epub
Rodriguez-Aznar, E., Wiesmüller, L., Sainz, Jr B., Hermann P. C. (2019). EMT and Stemness—Key Players in Pancreatic Cancer Stem Cells. Cancers (Basel). 11(8): 1136. https://doi: 10.3390/cancers11081136.
Razi, E., Radak, M., Mahjoubin-Tehran, M., Talebi, S., Shafiee, A., Hajighadimi, S., Moradizarmehri, S., Sharifi, H., Mousavi, N., Sarvizadeh, M., Nejati, M., Taghizadeh, M., Ghasemi, F. (2020). Cancer stem cells as therapeutic targets of pancreatic cancer. Fundam Clin Pharmacol. 34(2):202-212. https://doi: 10.1111/fcp.12521.
Patil, K., Khan, F.B., Akhtar, S., Ahmad, A., Uddin, Sh. (2021). The plasticity of pancreatic cancer stem cells: implications in therapeutic resistance. Cancer Metastasis Rev. 40(3): 691–720. https://doi: 10.1007/s10555-021-09979-x.
Gzil, A., Zarębska, I., Bursiewicz, W., Antosik, P., Grzanka, D., Szylberg, Ł. (2019). Markers of pancreatic cancer stem cells and their clinical and therapeutic implications. Molecular Biology Reports. 46:6629–6645 https://doi.org/10.1007/s11033-019-05058-1
Valle, S., Martin-Hijano, L., Alcalá, S., Alonso-Nocelo, M., Sainz, Jr. B. (2018). The Ever-Evolving Concept of the Cancer Stem Cell in Pancreatic Cancer. Cancers (Basel). 10(2): 33. https://doi: 10.3390/cancers10020033.
Barman, S., Fatima, I., Singh, A. B, Dhawan, P. (2021). Pancreatic Cancer and Therapy: Role and Regulation of Cancer Stem Cells. Int J Mol Sci. 30;22(9):4765. https://doi: 10.3390/ijms22094765.
Mu, W., Wang, Z., and Zöller, M. (2019). Ping-Pong—Tumor and Host in Pancreatic Cancer Progression. Front Oncol.; 9: 1359. https://doi: 10.3389/fonc.2019.01359.
Askan, G., Sahin, I.H., Chou, J.F. (2021). Pancreatic cancer stem cells may define tumor stroma characteristics and recurrence patterns in pancreatic ductal adenocarcinoma. BMC Cancer.;21(1):385. https://doi: 10.1186/s12885-021-08123-w. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
López de Andrés, J., Griñán-Lisón, C., Jiménez, G. Carmen; Jiménez, G.; Marchal C., Juan, A. (2020). Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment. Journal of Hematology and Oncology. 13(1):136. https://doi: 10.1186/s13045-020-00966-3. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
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