Epithelial-mesenchymal transition and stem cells in colorectal cancer progression
DOI:
https://doi.org/10.12775/JEHS.2020.10.10.018Keywords
Colorectal Cancer, Epithelial-Mesenchymal Transition, CD44 Antigen, Aldehyde Dehydrogenase 1Abstract
Introduction. Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide. Studying invasion and metastasizing mechanisms in colorectal carcinogenesis is gaining momentum. The purpose of the study was to analyze immunohistochemical (IHC) expression levels of epithelial and mesenchymal phenotypic markers, as well as cancer stem cells markers on I-IV (pTNM) stages of CRC. Materials and methods. Histopathological and IHC studies of 53 CRC were conducted. IHC study was carried out using antibodies against E-cadherin, CK-20, α-SMA, vimentin, CD44, and ALDH1. Results. CRC is characterized by low E-cadherin expression level that decreases during the I-IV stages sequence and by medium CK-20 expression level that decreases during the studied sequence. Furthermore, CRC is characterized by medium α-SMA and vimentin expression levels that increase during the studied sequence. These findings indicate parallel epithelial phenotype losing and mesenchymal phenotype acquiring by the cancer cells that happen during colorectal adenocarcinoma progression from the I to the IV stages. CD44 expression by the tumor stromal cells was described in this study. The median of CD44+ cells area equal to 61,26 (42,58; 79,15) % of CRC stromal cells. This index significantly increases from the I to the III stages of the tumor. ALDH1 expression by both cancer cells and stromal cells was described as well. The median of ALDH1+ stromal cells area equal to 40,22 (22,54; 47,77) %, the median of ALDH1+ cancer cells area equal to 42,15 (32,06; 50,42) %. The index of ALDH1+ stromal cells area significantly increases from the I to the III stages of the tumor whereas the index of ALDH1+ cancer cells area significantly increases from the III to the IV stages of the tumor. Moreover, correlations between the studied markers expression were revealed that proves the connection between epithelial-mesenchymal transition and stemness acquisition in CRC progression.
References
Mármol, I., Sánchez-de-Diego, C., Pradilla Dieste, A., Cerrada, E., Rodriguez Yoldi, M. J. (2017) Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer. International Journal of Molecular Sciences, 18(1): E197. https://doi.org/10.3390/ijms18010197
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
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
Ribatti, D., Tamma, R., Annese, T. (2020) Epithelial-Mesenchymal Transition in Cancer: A Historical Overview. Translational Oncology, 13(6): 100773. https://doi.org/10.1016/j.tranon.2020.100773.
Meyer, S.N., Galvan, J.A., Zahnd, S., Sokol, L., Dawson, H., Lugli, A., Zlobec, I. (2019) Co-expression of cytokeratin and vimentin in colorectal cancer highlights a subset of tumor buds and an atypical cancer-associated stroma. Human Pathology, 87: 18-27. https://doi.org/10.1016/j.humpath.2019.02.002
Wong, S.H.M., Fang, C.M., Chuah, L.H., Leong, C.O., Ngai, S.C. (2018) E-cadherin: Its dysregulation in carcinogenesis and clinical implications. Critical Reviews in Oncology/Hematology, 121: 11-22. https://doi.org/10.1016/j.critrevonc.2017.11.010
Al-Maghrabi, J., Emam, E., Gomaa, W. (2018) Immunohistochemical staining of cytokeratin 20 and cytokeratin 7 in colorectal carcinomas: Four different immunostaining profiles. Saudi Journal of Gastroenterology, 24 (2): 129-134. https://doi.org/doi: 10.4103/sjg.SJG_465_17
Fei, F., Li, C., Cao, Y., Liu, K., Du, J., Gu, Y., Wang, X., Li, Y., Zhang, S. (2019) CK7 expression associates with the location, differentiation, lymph node metastasis, and the Dukes' stage of primary colorectal cancers. Journal of Cancer, 10 (11): 2510-2519. https://doi.org/10.7150/jca.29397
Danielsson, F., Peterson, M.K., Caldeira Araújo, H., Lautenschläger, F., Gad, A.K.B. (2018) Vimentin Diversity in Health and Disease. Cells, 7(10): 147. https://doi.org/10.3390/cells7100147
Toiyama, Y., Yasuda, H., Saigusa, S., Tanaka, K., Inoue, Y., Goel, A., Kusunoki, M. (2013) Increased expression of Slug and Vimentin as novel predictive biomarkers for lymph node metastasis and poor prognosis in colorectal cancer. Carcinogenesis, 34(11): 2548‐2557. https://doi.org/10.1093/carcin/bgt282
Son, G.M., Kwon, M.S., Shin, D.H., Shin, N., Ryu, D., Kang, C.D. (2019) Comparisons of cancer-associated fibroblasts in the intratumoral stroma and invasive front in colorectal cancer. Medicine (Baltimore), 98 (18): e15164. https://doi.org/10.1097/MD.0000000000015164
Hanley, C.J., Noble, F., Ward, M., Bullock, M., Drifka, C., Mellone, M. (2016) A subset of myofibroblastic cancer-associated fibroblasts regulate collagen fiber elongation, which is prognostic in multiple cancers. Oncotarget, 7: 6159–74. https://doi.org/10.18632/oncotarget.6740
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
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
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