Significance of CD44- and ALDH1-positive stem cells in сolorectal adenocarcinoma progression

Authors

  • M. A. Shyshkin Zaporizhzhіa State Medical University, Ukraine,
  • V. O. Tumanskyi Zaporizhzhia State Medical University, Ukraine,
  • T. O. Khrystenko Zaporizhzhіa State Medical University, Ukraine,

DOI:

https://doi.org/10.14739/2310-1237.2020.2.212819

Keywords:

Сolorectal сancer, CD44 antigen, aldehyde dehydrogenase 1, cell proliferation, apoptosis

Abstract

 

Aim – to analyze CD44 and ALDH1 immunohistochemical expression levels, as well as their correlations with proliferative and apoptotic activity of cancer cells in colorectal adenocarcinoma (CRA) of stages I–IV (pTNM).

Materials and methods. Pathohistological and immunohistochemical studies of surgical material from 30 patients who underwent surgical treatment of colorectal adenocarcinoma (stages I–IV) were carried out.

Results. It was established that colorectal adenocarcinoma is characterized by membranous and cytoplasmic CD44 expression in stromal cells (the area of immunopositive cells in CRA = 61.26 (42.58; 79.15) %), the area taken by the cells significantly increases during the tumor progression from stage I to stage III and directly correlates with the depth of the tumor invasion, as well as the presence of regional and distant metastases. Colorectal adenocarcinoma is characterized by cytoplasmic ALDH1 expression in the tumor stomal cells; the area of immunopositive cells in CRA = 40.22 (22.54; 47.77) % and significantly increases during the tumor progression from stage II to stage IV, as well as directly correlates with the depth of its invasion. Cytoplasmic ALDH1 expression in cancer cells of colorectal cancer was also revealed; the area of immunopositive cancer cells in CRA = 42.15 (32.06; 50.42) %. The area of immunopositive cancer cells significantly increases during the tumor progression from stage III to stage IV and directly correlates with each of the pTNM indexes. The correlation analysis of the indexes obtained for studied markers, as well as the markers of proliferation and apoptosis, made possible to reveal the next tendencies: the increasing area of CD44-possitive stromal cells in CRA is associated with decreasing cancer cells proliferation level, and also with the activation of epithelial-to-mesenchymal transition; the increasing area of ALDH1-possitive stromal cells is associated with decreasing cancer cells apoptosis level.

Conclusions. The area of CD44-positive stromal cells significantly increases with the tumor progression from stage I to stage III and is associated with decreasing of the cancer cells proliferation level. The area of ALDH1-positive stromal cells significantly increases with tumor progression from stage II to stage IV and is associated with decreasing of the cancer cells apoptosis level, while the area of ALDH1-positive cancer cells significantly increases with tumor progression from stage III to stage IV.

References

Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 68(6), 394-424. https://doi.org/10.3322/caac.21492

Rawla, P., Sunkara, T., & Barsouk, A. (2019). Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Przeglad gastroenterologiczny, 14(2), 89-103. https://doi.org/10.5114/pg.2018.81072

Tumanskyi, V. O., & Kovalenko, I. S. (2019). Rakovye stvolovye i mezenkhimal'nye stvolove kletki v protokovoi adenokartsinome podzheludochnoi zhelezy [Cancer stem cells and mesenchymal stem cells in pancreatic ductal adenocarcinoma]. Pathologia, 16(1), 131-138. [in Russian]. https://doi.org/10.14739/2310-1237.2019.1.166476

Moharil, R. B., Dive, A., Khandekar, S., & Bodhade, A. (2017). Cancer stem cells: An insight. Journal of oral and maxillofacial pathology : JOMFP, 21(3), 463. https://doi.org/10.4103/jomfp.JOMFP_132_16

Najafi, M., Farhood, B., & Mortezaee, K. (2019). Cancer stem cells (CSCs) in cancer progression and therapy. Journal of cellular physiology, 234(6), 8381-8395. https://doi.org/10.1002/jcp.27740

Najafi, M., Mortezaee, K., & Majidpoor, J. (2019). Cancer stem cell (CSC) resistance drivers. Life sciences, 234, 116781. https://doi.org/10.1016/j.lfs.2019.116781

Zhou, Y., Xia, L., Wang, H., Oyang, L., Su, M., Liu, Q., Lin, J., Tan, S., Tian, Y., Liao, Q., & Cao, D. (2017). Cancer stem cells in progression of colorectal cancer. Oncotarget, 9(70), 33403-33415. https://doi.org/10.18632/oncotarget.23607

Morath, I., Hartmann, T. N., & Orian-Rousseau, V. (2016). CD44: More than a mere stem cell marker. The international journal of biochemistry & cell biology, 81(Pt A), 166-173. https://doi.org/10.1016/j.biocel.2016.09.009

Wang, L., Zuo, X., Xie, K., & Wei, D. (2018). The Role of CD44 and Cancer Stem Cells. Methods in molecular biology, 1692, 31-42. https://doi.org/10.1007/978-1-4939-7401-6_3

Chen, C., Zhao, S., Karnad, A., & Freeman, J. W. (2018). The biology and role of CD44 in cancer progression: therapeutic implications. Journal of hematology & oncology, 11(1), 64. https://doi.org/10.1186/s13045-018-0605-5

Senbanjo, L. T., & Chellaiah, M. A. (2017). CD44: A Multifunctional Cell Surface Adhesion Receptor Is a Regulator of Progression and Metastasis of Cancer Cells. Frontiers in cell and developmental biology, 5, 18. https://doi.org/10.3389/fcell.2017.00018

Xia, P., & Xu, X. Y. (2016). Prognostic significance of CD44 in human colon cancer and gastric cancer: Evidence from bioinformatic analyses. Oncotarget, 7(29), 45538-45546. https://doi.org/10.18632/oncotarget.9998

Inoue, K., & Fry, E. A. (2015). Aberrant Splicing of Estrogen Receptor, HER2, and CD44 Genes in Breast Cancer. Genetics & epigenetics, 7, 19-32. https://doi.org/10.4137/GEG.S35500

Vassalli, G. (2019). Aldehyde Dehydrogenases: Not Just Markers, but Functional Regulators of Stem Cells. Stem cells international, 2019, 3904645. https://doi.org/10.1155/2019/3904645

Singh, S., Arcaroli, J., Thompson, D. C., Messersmith, W., & Vasiliou, V. (2015). Acetaldehyde and retinaldehyde-metabolizing enzymes in colon and pancreatic cancers. Advances in experimental medicine and biology, 815, 281-294. https://doi.org/10.1007/978-3-319-09614-8_16

Ma, F., Li, H., Li, Y., Ding, X., Wang, H., Fan, Y., Lin, C., Qian, H., & Xu, B. (2017). Aldehyde dehydrogenase 1 (ALDH1) expression is an independent prognostic factor in triple negative breast cancer (TNBC). Medicine, 96(14), e6561. https://doi.org/10.1097/MD.0000000000006561

Chen, J., Xia, Q., Jiang, B., Chang, W., Yuan, W., Ma, Z., Liu, Z., & Shu, X. (2015). Prognostic Value of Cancer Stem Cell Marker ALDH1 Expression in Colorectal Cancer: A Systematic Review and Meta-Analysis. PloS one, 10(12), e0145164. https://doi.org/10.1371/journal.pone.0145164

Shyshkin, M. A. (2016). Sravnitel'naya immunogistokhimicheskaya kharakteristika proliferatsii i apoptoza kolorektal'noi adenokartsinomy [Comparative immunohistochemical study of proliferation and apoptosis in colorectal adenocarcinoma]. Pathologia, (3), 65-72. [in Russian]. https://doi.org/10.14739/2310-1237.2016.3.87497

Shyshkin, M. A. (2018). Molekulyarno-immunogistokhimicheskaya kharakteristika proliferatsii i apoptoza opukholevykh kletok kolorektal'noi adenokartsinomy [Molecular-immunohistochemical characteristics of proliferation and apoptosis of tumor cells in colorectal adenocarcinoma]. Pathologia, 15(1), 49-56. [in Russian]. https://doi.org/10.14739/2310-1237.2018.1.129447

Vishnubalaji, R., Manikandan, M., Fahad, M., Hamam, R., Alfayez, M., Kassem, M., Aldahmash, A., & Alajez, N. M. (2018). Molecular profiling of ALDH1+ colorectal cancer stem cells reveals preferential activation of MAPK, FAK, and oxidative stress pro-survival signalling pathways. Oncotarget, 9(17), 13551-13564. https://doi.org/10.18632/oncotarget.24420

Mahmood, N. A., Abdulghany, Z. S., & Al-Sudani, I. M. (2018). Expression of Aldehyde Dehydrogenase (ALDH1) and ATP Binding Cassette Transporter G2 (ABCG2) in Iraqi Patients with Colon Cancer and the Relation with Clinicopathological Features. International journal of molecular and cellular medicine, 7(4), 234-240. https://doi.org/10.22088/IJMCM.BUMS.7.4.234

Holah, N. S., Aiad, H. A., Asaad, N. Y., Elkhouly, E. A., & Lasheen, A. G. (2017). Evaluation of the Role of ALDH1 as Cancer Stem Cell Marker in Colorectal Carcinoma: An Immunohistochemical Study. Journal of clinical and diagnostic research : JCDR, 11(1), EC17-EC23. https://doi.org/10.7860/JCDR/2017/22671.9291

van der Waals, L. M., Borel Rinkes, I., & Kranenburg, O. (2018). ALDH1A1 expression is associated with poor differentiation, 'right-sidedness' and poor survival in human colorectal cancer. PloS one, 13(10), e0205536. https://doi.org/10.1371/journal.pone.0205536

Shyshkin, M. A., & Khrystenko, T. O. (2019). Distal colonic polyps: immunohistochemical study of proliferation and apoptosis. Morphologia, 13(1), 67-75. https://doi.org/10.26641/1997-9665.2019.1.67-75

Preca, B. T., Bajdak, K., Mock, K., Sundararajan, V., Pfannstiel, J., Maurer, J., Wellner, U., Hopt, U. T., Brummer, T., Brabletz, S., Brabletz, T., & Stemmler, M. P. (2015). A self-enforcing CD44s/ZEB1 feedback loop maintains EMT and stemness properties in cancer cells. International journal of cancer, 137(11), 2566-2577. https://doi.org/10.1002/ijc.29642

Tian, S., Liu, D. H., Wang, D., Ren, F., & Xia, P. (2018). Aldehyde Dehydrogenase 1 (ALDH1) Promotes the Toxicity of TRAIL in Non-Small Cell Lung Cancer Cells via Post-Transcriptional Regulation of MEK-1 Expression. Cellular physiology and biochemistry, 51(1), 217-227. https://doi.org/10.1159/000495202

Wu, A., Luo, W., Zhang, Q., Yang, Z., Zhang, G., Li, S., & Yao, K. (2013). Aldehyde dehydrogenase 1, a functional marker for identifying cancer stem cells in human nasopharyngeal carcinoma. Cancer letters, 330(2), 181-189. https://doi.org/10.1016/j.canlet.2012.11.046

Lazennec, G., & Lam, P. Y. (2016). Recent discoveries concerning the tumor - mesenchymal stem cell interactions. Biochimica et biophysica acta, 1866(2), 290-299. https://doi.org/10.1016/j.bbcan.2016.10.004

Berger, L., Shamai, Y., Skorecki, K. L., & Tzukerman, M. (2016). Tumor Specific Recruitment and Reprogramming of Mesenchymal Stem Cells in Tumorigenesis. Stem cells, 34(4), 1011-1026. https://doi.org/10.1002/stem.2269

How to Cite

1.
Shyshkin MA, Tumanskyi VO, Khrystenko TO. Significance of CD44- and ALDH1-positive stem cells in сolorectal adenocarcinoma progression. Pathologia [Internet]. 2020Sep.28 [cited 2024Nov.23];(2). Available from: http://pat.zsmu.edu.ua/article/view/212819

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Section

Original research