DOWN-REGULATION OF ALDH1A1 INCREASED EXPRESSION OF CARCINOGENESIS-RELATED GENES IN NON-SMALL CELL LUNG CANCER CELL LINE OF A549
DOI:
https://doi.org/10.11113/jt.v78.9866Keywords:
Lung cancer, cancer stem cell, CD166 /EpCAM and CD166 /CD44Abstract
Purpose: This study was aimed to isolate the putative cancer stem cell (CSC) populations from A549 lung cancer cell line and to evaluate the difference of carcinogenesis-related genes expression within parental population (A549) and isolated CSC populations (A549 CD166+ /EpCAM+ and CD166+ /CD44+). Methods: We performed flow cytometry analysis to sort out cell positive for these markers; CD166+ /EpCAM + and CD166+ /CD44+ from A549 cancer cell line. The isolated cells were tested for multipotent capacities by clonogenic and differentiation assays. Quantitative real time PCR was performed for both isolated CSC population and parental population to test expression of ALDH1A1 and 6 other genes that known to contribute to carcinogenesis; RARβ CYP24A1, BIRC5, EDN1, IL1β and PTGS2. Result(s): Both CD166+ /EpCAM+ and CD166+ /CD44+ have ability to form colonies and able to differentiate into adipocytes and osteocyte. Expression of ALDH1A1 was downregulated in all three cell populations (parental A549, A549 CD166+ /EpCAM+ and A549 CD166+ /CD44+) whereas the other 6 carcinogenesis-related genes were upregulated in all three cancer cell populations. There are no significant differences of gene expressions were detected among all three populations (p > 0.05). Conclusion(s): Downregulation of ALDH1A1 in all three cancer populations up-regulate the expression of other 6 carcinogenesis-related genes. Gene regulations between parental cancer cell (A549) and both putative CSC populations show no significant difference suggesting the existence of various CSC subpopulations reside within parental A549 populationReferences
Omar, Z., Ibrahim Tamin, N. 2011. National Cancer Registry Report: Malaysia Cancer Statistics-Data and Figure. Malaysia: National Cancer Registry: 85-87.
Jemal, A., Siegel, R., Ward, E., Murray, T., Xu, J., Smigal, C., Thun, M.J. 2006: Cancer Statistics, 2006. CA: A Cancer Journal for Clinicians. 56(2):106-130.
Eramo, A., Lotti, F., Sette, G., Pilozzi, E., Biffoni, M., Di Virgilio, A., Conticello, C., Ruco, L., Peschle, C., De Maria, R. 2008. Identification and Expansion of The Tumorigenic Lung Cancer Stem Cell Population. Cell Death & Differentiation. 15(3):504-514.
Collins, L.G., Haines, C., Perkel, R., Enck, R.E. 2007. Lung Cancer: Diagnosis and Management. Am Fam Physician. 75(1):56-63.
Puglisi, M.A., Tesori, V., Lattanzi, W., Gasbarrini, G.B., Gasbarrini, A. 2013. Colon Cancer Stem Cells: Controversies and Perspectives. World Journal of Gastroenterology: WJG. 19(20):2997.
Rich J, N., Bao, S. 2007. Chemotherapy and Cancer Stem Cells. Cell Stem Cell. 1(4):353-355.
Ni, J., Cozzi, P., Hao, J., Beretov, J., Chang, L., Duan, W., Shigdar, S., Delprado, W., Graham, P., Bucci, J. 2013. Epithelial Cell Adhesion Molecule (EpCAM) is Associated with Prostate Cancer Etastasis and Chemo/Radioresistance via The PI3K/Akt/mTOR Signaling Pathway. The International Journal of Biochemistry & Cell Biology. 45(12):2736-2748.
Seimetz, D., Lindhofer, H., Bokemeyer, C. 2010. Development and Approval of The Trifunctional Antibody Catumaxomab (Anti-EpCAM× Anti-CD3) as A Targeted Cancer Immunotherapy. Cancer Treatment Reviews. 36(6):458-467.
Munz, M., Baeuerle, P.A., Gires, O. 2009. The Emerging Role of EpCAM in Cancer and Stem Cell Signaling. Cancer Research. 69(14): 5627-5629.
Langan, R.C., Mullinax, J.E., Raiji, M.T., Upham, T., Summers, T., Stojadinovic, A., Avital, I. 2013. Colorectal Cancer Biomarkers and The Potential Role of Cancer Stem Cells. J Cancer. 4(3):241-250.
Coppola, D., Hyacinthe, M., Fu, L., Cantor, A.B., Karl, R., Marcet, J., Cooper, D.L., Nicosia, S.V., Cooper, H.S. 1998. CD44V6 Expression in Human Colorectal Carcinoma. Human Pathology. 29(6):627-635.
Du, L., Wang, H., He, L., Zhang, J., Ni, B., Wang, X., Jin, H., Cahuzac, N., Mehrpour, M., Lu, Y. 2008. CD44 is of Functional Importance for Colorectal Cancer Stem Cells. Clinical Cancer Research. 14(21):6751-6760.
Piyathilake, C.J., Frost, A.R., Weiss, H., Manne, U., Heimburger, D.C., Grizzle, W.E. 2000. The Expression of Ep-CAM (17-1 A) in Squamous Cell Cancers of The Lung. Human Pathology. 31(4):482-487.
Dalerba, P., Dylla, S.J., Park, I.K., Liu, R., Wang, X., Cho, R.W., Hoey, T., Gurney, A., Huang, E.H., Simeone, D.M., Shelton, A.A., Parmiani, G., Castelli, C., Calrke, M.F. 2007. Phenotypic Characterization of Human Colorectal Cancer Stem Cells. Proceedings of The National Academy of Sciences of The United States of America. 104(24):10158-10163.
Collins, A.T., Berry, P.A., Hyde, C., Stower, M.J., Maitland, N.J. 2005. Prospective Identification of Tumorigenic Prostate Cancer Stem Cells. Cancer Res. 65(23):10946-10951.
Ruck, P., Wichert, G., Handgretinger, R., Kaiserling, E. 2000. Epâ€CAM in Malignant Liver Tumours. The Journal of Pathology, 191(1):102-103.
de Boer, C.J., van Krieken, J.H., Janssenâ€van Rhijn, C.M., Litvinov, S.V. 1999. Expression of Epâ€CAM in Normal, Regenerating, Metaplastic, and Neoplastic Liver. The Journal of Pathology. 188(2): 201-206.
Li, M., Song, S., Lippman, S.M., Zhang, X-k., Liu, X., Lotan, R., Xu, X-C. 2002. Induction of Retinoic Acid Receptor-beta Suppresses Cyclooxygenase-2 Expression in Esophageal Cancer Cells. Oncogene. 21(3): 411-418.
Prince, M., Sivanandan, R., Kaczorowski, A., Wolf, G., Kaplan, M., Dalerba, P., Weissman, I., Clarke, M., Ailles, L. 2007. Identification of A Subpopulation of Cells with Cancer Stem Cell Properties in Head and Neck Squamous Cell Carcinoma. Proceedings of the National Academy of Sciences, 104(3):973-978.
Li, C., Heidt, D.G., Dalerba, P., Burant, C.F., Zhang, L., Adsay, V., Wicha, M., Clarke, M.F., Simeone, D.M. 2007. Identification of Pancreatic Cancer Stem Cells. Cancer Research. 67(3):1030-1037.
Okudela, K., Woo, T., Mitsui, H., Suzuki, T., Tajiri, M., Sakuma, Y., Miyagi, Y., Tateishi, Y., Umeda, S., Masuda, M. 2013. Downregulation of ALDH1A1 Expression in Non-small Cell Lung Carcinomas–Its Clinicopathologic and Biological Significance. International Journal of Clinical and Experimental Pathology. 6(1):1.
Mita, A.C., Mita, M.M., Nawrocki, S.T., Giles, F.J. 2008. Survivin: Key Regulator of Mitosis and Apoptosis and Novel Target for Cancer Therapeutics. Clinical Cancer Research. 14(16):5000-5005.
Wang, C., Xie, J., Guo, J., Manning, H.C., Gore, J.C., Guo, N. 2012. Evaluation of CD44 and CD133 as Cancer Stem Cell Markers for Colorectal Cancer. Oncology Reports. 28(4):1301-1308.
Zhang, M., Zhang, X., Bai, C-X., Chen, J., Wei, M. 2004. Inhibition of Epidermal Growth Factor Receptor Expression by RNA Interference in A549 Cells. Acta Pharmacol Sin. 25(1):61-67.
Sullivan, J.P., Minna, J.D., Shay, J.W. 2010. Evidence for Self-Renewing Lung Cancer Stem Cells and Their Implications in Tumor Initiation, Progression, and Targeted Therapy. Cancer and Metastasis Reviews. 29(1):61-72.
Zakaria, N., Yusoff, N.M., Zakaria, Z., Lim, M.N., Baharuddin, P.J.N., Fakiruddin, K.S., Yahaya, B. 2015. Human Non-small Cell Lung Cancer Expresses Putative Cancer Stem Cell Markers and Exhibits The Transcriptomic Profile of Multipotent Cells. BMC Cancer. 15(1):84.
Alamgeer, M., Peacock, C.D., Matsui, W., Ganju, V., Watkins, D.N. 2013. Cancer Stem Cells in Lung Cancer: Evidence and Controversies. Respirology. 18(5):757-764.
Moreb, J.S., Baker, H.V., Chang, L-J., Amaya, M., Lopez, M.C., Ostmark, B., Chou, W. 2008. ALDH Isozymes Downregulation Affects Cell Growth, Cell Motility and Gene Expression in Lung Cancer Cells. Molecular Cancer. 7(1):1.
Jackson, B., Brocker, C., Thompson, D.C., Black, W., Vasiliou, K., Nebert, D.W., Vasiliou, V. 2011. Update on The Aldehyde Dehydrogenase Gene (ALDH) Superfamily. Human Genomics. 5(4):1.
Vasiliou, V., Nebert, D.W. 2005. Analysis and Update of The Human Aldehyde Dehydrogenase (ALDH) Gene Family. Human Genomics. 2(2):1.
Cheung, A., Wan, T., Leung, J., Chan, L., Huang, H., Kwong, Y., Liang, R., Leung, A. 2007. Aldehyde Dehydrogenase Activity in Leukemic Blasts Defines A Subgroup of Acute Myeloid Leukemia with Adverse Prognosis and Superior NOD/SCID Engrafting Potential. Leukemia. 21(7):1423-1430.
Li, X., Wan, L., Geng, J., Wu, C-L., Bai, X. 2012. Aldehyde Dehydrogenase 1A1 Possesses Stem-like Properties and Predicts Lung Cancer Patient Outcome. Journal of Thoracic Oncology. 7(8):1235-1245.
Steg, A.D., Bevis, K.S., Katre, A.A., Ziebarth, A., Dobbin, Z.C., Alvarez, R.D., Zhang, K., Conner, M., Landen, C.N. 2012. Stem Cell Pathways Contribute to Clinical Chemoresistance in Ovarian Cancer. Clinical Cancer Research. 18(3):869-881.
Downloads
Published
Issue
Section
License
Copyright of articles that appear in Jurnal Teknologi belongs exclusively to Penerbit Universiti Teknologi Malaysia (Penerbit UTM Press). This copyright covers the rights to reproduce the article, including reprints, electronic reproductions, or any other reproductions of similar nature.