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Published on: March 1, 2020
[Heterogeneity of ALDH1, CD133 and CD34 expression in cancer stem cells of lung adenocarcinoma]
E A Kogan1, E E Shchelokova1, T A Demura1
1Sechenov First Moscow State Medical University, Moscow, Russia.
Abstract:
Lung adenocarcinoma (LAC) is one of the leading causes of cancer mortality, which is most likely due to the presence of cancer stem cells (CSC) in the tumor, which form a heterogeneous hierarchy and are responsible for the occurrence and progression of carcinoma, as well as its unfavorable prognosis. The ability of CSC to form heterogeneous tumor populations in lung cancer has not been sufficiently studied.
Objective:
Detection of cancer cells with signs of stemness in LAC and establishment of their heterogeneity by expression of ALDH1, CD133 and CD34 markers in surgical material depending on the histological type, degree of malignancy and stage of the tumor process, as well as in the A549 cell culture.
Material And Methods:
Clinical and morphological analysis of surgical material of LAC from 32 patients was performed, and the culture of lung adenocarcinoma cells A549 was studied. Stem cell markers ALDH1, CD133 and CD34 were detected in the analyzed material by immunohistochemistry. The percentage of positively stained cells was calculated in the preparations.
Results:
In all cases of ALCL, CSCs containing ALDH1, CD133 and CD34 were found both in the surgical material and in the A549 cell culture. Heterogeneity of CSCs for the studied markers was established. In patients with early stages of cancer without metastases in the lymph nodes, the number of ALDH1+ CSCs predominated in the primary tumor tissue. With the appearance of metastases in the regional lymph nodes, a significant increase in the number of cells with positive staining in reactions with antibodies to CD34 was found in the ALCL tissue. In patients with metastatic cancer, staining of the overwhelming majority of tumor cells was detected in reactions with all markers - ALDH1, CD133 and CD34.
Conclusion:
In ACL, both in the surgical material and in the A549 culture, CSCs expressing the stemness markers ALDH1, CD133 and CD34 were detected. An increase in the number of CSCs expressing the stemness markers ALDH1, CD34 and CD133 in the tumor tissue occurs with carcinoma progression. In ACL, heterogeneity of CSCs by the studied markers is noted: at early stages in patients without metastases in the lymph nodes, ALDH1+ CSCs predominate in the tumor tissue, while with the appearance of metastatic lesions of the lymph nodes, CD34+ CSC populations dominate. Quantitative heterogeneity is also observed in the A549 cell culture: the largest number was CD34+ CSCs, slightly less ALDH1+ CSCs and a minimum number of cells with CD133+ CSCs.
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