ISSN 0564-3783  



Main page
Contacts
Themes
Archive  
Themes
Subscription
Information to authors
Editorial board
Mobile version


In Ukrainian

Export citations
UNIMARC
BibTeX
RIS





REDUCED EXPRESSION OF PEDF AND ALDH1A1 DURING SPHEROID TRANSITION OF LUNG CANCER CELLS: AN IN VITRO STUDY

TERZI M.Y., OKUYAN H.M., DURAN G.G., KÜÇÜK M.U.

 




Cancer stem cells (CSCs), can initiate tumorigenesis and metastasis and show resistance against chemotherapy owing to the expression of prominent stem cell markers. CSCs are a subpopulation of highly heterogenic cancer spheroid cells. Pigment epithelium-derived factor (PEDF) is a neurotrophic, anti-tumorigenic, and anti-metastatic protein and its gene expression levels in A549 spheroids is still unknown. We aimed to compare clonogenicity and mRNA levels of PEDF, Oct4, and ALDH1A1 between A549 and spheroid cells. Spheroid and colony formation assays were performed with spheroid and A549 cells. We performed quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for gene expression analysis. The clonogenic ratios for A549 and spheroids were ~60% and ~1% respectively. During spheroid formation, Oct4 mRNA level did not change but PEDF and ALDH1A1 levels decreased significantly. CSCs are characterized by elevated stem cell markers but spheroid cells consist of heterogeneous population including CSCs. In spheroid population, no increase in stem cell markers was observed. The reduced PEDF levels during spheroid transition can be a suppression mechanism of spheroid cells.

Key words: lung cancer, PEDF, A549, spheroid cell, Oct4, ALDH1A1

Tsitologiya i Genetika 2022, vol. 56, no. 2, pp. 70-72

  1. Department of Medical Biology, Faculty of Medicine, Hatay Mustafa Kemal University, Hatay, Turkey
  2. Department of Molecular Biochemistry and Genetics, Graduate School of Health Sciences, Hatay Mustafa Kemal University, Hatay, Turkey
  3. Department of Medical Services and Techniques, Vocational School of Health Services, Hatay Mustafa Kemal University, Hatay, Turkey
  4. Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Sakarya University of Applied Sciences, Sakarya, Turkey

E-mail: yusufterzi gmailcom, myterzi mku.edu.tr

TERZI M.Y., OKUYAN H.M., DURAN G.G., KÜÇÜK M.U. REDUCED EXPRESSION OF PEDF AND ALDH1A1 DURING SPHEROID TRANSITION OF LUNG CANCER CELLS: AN IN VITRO STUDY, Tsitol Genet., 2022, vol. 56, no. 2, pp. 70-72.

In "Cytology and Genetics":
M. Y. Terzi, H. M. Okuyan, G. Gülbol-Duran & M. Urhan-Küçük Reduced Expression of PEDF and ALDH1A1 during Spheroid Transition of Lung Cancer Cells: An In Vitro Study, Cytol Genet., 2022, vol. 56, no. 2, pp. 172178
DOI: 10.3103/S0095452722020104


References

Adhikari, A.S., Agarwal, N., Wood, B.M., et al., CD117 and Stro-1 identify osteosarcoma tumor-initiating cells associated with metastasis and drug resistance, Cancer Res., 2010, vol. 70, no. 11, pp. 46024612. https://doi.org/10.1158/0008-5472.CAN-09-3463

Allegra, A., Alonci, A., Penna, G., et al., The cancer stem cell hypothesis: a guide to potential molecular targets, Cancer Invest., 2014, vol. 32, pp. 470495. https://doi.org/10.3109/07357907.2014.958231

Belkacemi, L. and Zhang, S.X., Anti-tumor effects of pigment epithelium-derived factor (PEDF): implication for cancer therapy. A mini-review, J. Exp. Clin. Cancer Res., 2016, vol. 35, art. ID 4. https://doi.org/10.1186/s13046-015-0278-7

Bonnet, D. and Dick, J.E., Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell, Nat. Med., 1997, vol. 3, pp. 730737.

Bouck, N., PEDF: anti-angiogenic guardian of ocular function, Trends Mol. Med., 2002, vol. 8, pp. 330-334.

Chen, J., Ye, L., Zhang, L., et al., The molecular impact of pigment epithelium-derived factor, PEDF, on lung cancer cells and the clinical significance, Int. J. Oncol., 2009, vol. 35, pp. 159166. https://doi.org/10.3892/ijo_00000324

Chen, Y.C., Hsu, H.S., Chen, Y.W., et al., Oct-4 expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells, PLoS One, 2008, vol. 3, art. ID e2637. https://doi.org/10.1371/journal.pone.0002637

Cheng, Y.H., Chen, Y.C., Brien, R., et al., Scaling and automation of a high-throughput single-cell-derived tumor sphere assay chip, Lab. Chip., 2016, vol. 16, pp. 37083717. https://doi.org/10.1039/c6lc00778c

Demestre, M., Terzi, M.Y., Mautner, V., et al., Effects of pigment epithelium derived factor (PEDF) on malignant peripheral nerve sheath tumors (MPNSTs), J. Neurooncol., 2013, vol. 115, pp. 391399. https://doi.org/10.1007/s11060-013-1252-x

Dimou, A., Neumeister, V., Agarwal, S., et al., Measurement of aldehyde dehydrogenase 1 expression defines a group with better prognosis in patients with non-small cell lung cancer, Am. J. Pathol., 2012, vol. 181, pp. 1436-1442. https://doi.org/10.1016/j.ajpath.2012.06.037

Duru, N., Candas, D., Jiang, G., et al., Breast cancer adaptive resistance: HER2 and cancer stem cell repopulation in a heterogeneous tumor society, J. Cancer Res. Clin. Oncol., 2014, vol. 140, pp. 114. https://doi.org/10.1007/s00432-013-1494-1

Eramo, A., Lotti, F., Sette, G., et al., Identification and expansion of the tumorigenic lung cancer stem cell population, Cell Death Differ., 2008, vol. 15, pp. 504-514. https://doi.org/10.1038/sj.cdd.4402283

Eyler, C.E. and Rich, J.N., Survival of the fittest: cancer stem cells in therapeutic resistance and angiogenesis, J. Clin. Oncol., 2008, vol. 26, no. 17, pp. 28392845. https://doi.org/10.1200/JCO.2007.15.1829

Fernandez-Garcia, N.I., Volpert, O.V., and Jimenez, B., Pigment epithelium-derived factor as a multifunctional antitumor factor, J. Mol. Med., 2007, vol. 85, pp. 1522. https://doi.org/10.1007/s00109-006-0111-z

Gradilone, A., Naso, G., Raimondi, C., et al., Circulating tumor cells (CTCs) in metastatic breast cancer (MBC): prognosis, drug resistance and phenotypic characterization, Ann. Oncol., 2011, vol. 22, no. 1, pp. 8692. doihttps://doi.org/10.1093/annonc/mdq323

Herreros-Pomares, A., de-Maya-Girones, J.D., Calabuig-Farinas, S., et al., Lung tumorspheres reveal cancer stem cell-like properties and a score with prognostic impact in resected non-small-cell lung cancer, Cell Death Dis., 2019, vol. 10, art. ID 660. https://doi.org/10.1038/s41419-019-1898-1

Hong, H., Zhou, T., Fang, S., et al., Pigment epithelium-derived factor (PEDF) inhibits breast cancer metastasis by down-regulating fibronectin, Breast Cancer Res. Treat., 2014, vol. 148, pp. 6172. https://doi.org/10.1007/s10549-014-3154-9

Jiang, F., Qiu, Q., Khanna, A., et al., Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer, Mol. Cancer Res., 2009, vol. 7, no. 3, pp. 330338. https://doi.org/10.1158/1541-7786.MCR-08-0393

Jordan, C.T., Cancer stem cell biology: from leukemia to solid tumors, Curr. Opin. Cell Biol., 2004, vol. 16, pp. 708712. https://doi.org/10.1016/j.ceb.2004.09.002

Kim, D., Choi, B.H., Ryoo, I.G., et al., High NRF2 level mediates cancer stem cell-like properties of aldehyde dehydrogenase (ALDH)-high ovarian cancer cells: inhibitory role of all-trans retinoic acid in ALDH/NRF2 signaling, Cell Death Dis., 2018, vol. 9, art. ID 896. https://doi.org/10.1038/s41419-018-0903-4

Lee, C.H., Yu, C.C., Wang, B.Y., et al., Tumorsphere as an effective in vitro platform for screening anti-cancer stem cell drugs, Oncotarget, 2016, vol. 7, pp. 12151226. https://doi.org/10.18632/oncotarget.6261

Li, D., Zhang, T., Gu, W., et al., The ALDH1(+) subpopulation of the human NMFH-1 cell line exhibits cancer stem-like characteristics, Oncol. Rep., 2015, vol. 33, pp. 22912298. https://doi.org/10.3892/or.2015.3842

Liu, J., Ma, L., Xu, J., et al., Spheroid body-forming cells in the human gastric cancer cell line MKN-45 possess cancer stem cell properties, Int. J. Oncol., 2013, vol. 42, pp. 453459. https://doi.org/10.3892/ijo.2012.1720

Massague, J. and Obenauf, A.C., Metastatic colonization by circulating tumour cells, Nature, 2016, vol. 529, pp. 298306. https://doi.org/10.1038/nature17038

Minkevich, N.I., Lipkin, V.M., and Kostanyan I.A., PEDFa noninhibitory serpin with neurotrophic activity, Acta Naturae, 2010, vol. 2, pp. 6271.

Morrison, B.J., Steel, J.C., and Morris, J.C., Sphere culture of murine lung cancer cell lines are enriched with cancer initiating cells, PLoS One, 2012, vol. 7, art. ID e49752. https://doi.org/10.1371/journal.pone.0049752

Nwani, N.G., Deguiz, M.L., Jimenez, B., et al., Melanoma cells block PEDF production in fibroblasts to induce the tumor-promoting phenotype of cancer-associated fibroblasts, Cancer Res., 2016, vol. 76, pp. 22652276. https://doi.org/10.1158/0008-5472.CAN-15-2468

Pang, L., Ding, J., Ge, Y., et al., Single-cell-derived tumor-sphere formation and drug-resistance assay using an integrated microfluidics, Anal. Chem., 2019, vol. 91, pp. 83188325. https://doi.org/10.1021/acs.analchem.9b01084

Patel, M., Lu, L., Zander, D.S., et al., ALDH1A1 and ALDH3A1 expression in lung cancers: Correlation with histologic type and potential precursors, Lung Cancer, 2008, vol. 59, pp. 340349. https://doi.org/10.1016/j.lungcan.2007.08.033

Qureshi-Baig, K., Ullmann, P., Rodriguez, F., et al., What do we learn from spheroid culture systems? Insights from tumorspheres derived from primary colon cancer tissue, PLoS One, 2016, vol. 11, art. ID e0146052. https://doi.org/10.1371/journal.pone.0146052

Ribaux, P., Britan, A., Thumann, G., et al., Malignant ascites: a source of therapeutic protein against ovarian cancer?, Oncotarget, 2019, vol. 10, pp. 58945905. https://doi.org/10.18632/oncotarget.27185

Roudi, R., Madjd, Z., Ebrahimi, M., et al., CD44 and CD24 cannot act as cancer stem cell markers in human lung adenocarcinoma cell line A549, Cell. Mol. Biol. Lett., 2014, vol. 19, pp. 2336. https://doi.org/10.2478/s11658-013-0112-1

Seo, D.C., Sung, J.M., Cho, H.J., et al., Gene expression profiling of cancer stem cell in human lung adenocarcinoma A549 cells, Mol. Cancer, 2007, vol. 6, art. ID 75. https://doi.org/10.1186/1476-4598-6-75

Singh, A.K., Arya, R.K., Maheshwari. S., et al., Tumor heterogeneity and cancer stem cell paradigm: updates in concept, controversies and clinical relevance, Int. J. Cancer, 2015, vol. 136, pp. 19912000. https://doi.org/10.1002/ijc.28804

Sladek, N.E., Human aldehyde dehydrogenases: Potential pathological, pharmacological, and toxicological impact, J. Biochem. Mol. Toxicol., 2003, vol. 17, pp. 723. https://doi.org/10.1002/jbt.10057

Sourisseau, T., Hassan, K.A., Wistuba, I., et al., Lung cancer stem cell: fancy conceptual model of tumor biology or cornerstone of a forthcoming therapeutic breakthrough?, J. Thorac. Oncol., 2014, vol. 9, pp. 717. https://doi.org/10.1097/JTO.0000000000000028

Spyra, M., Kluwe, L., Hagel, C., et al., Cancer stem cell-like cells derived from malignant peripheral nerve sheath tumors, PLoS One, 2011, vol. 6, art. ID e21099. https://doi.org/10.1371/journal.pone.0021099

Sung, J.M., Cho, H.J., Yi, H., et al., Characterization of a stem cell population in lung cancer A549 cells, Biochem. Biophys. Res. Commun., 2008, vol. 371, no. 1, pp. 163167. https://doi.org/10.1016/j.bbrc.2008.04.038

Teng, Y., Wang, X., Wang, Y., et al., Wnt/β-catenin signaling regulates cancer stem cells in lung cancer A549 cells, Biochem. Biophys. Res. Commun., 2010, vol. 392, no. 3, pp. 373379. https://doi.org/10.1016/j.bbrc.2010.01.028

Terzi, M.Y., Casalis, P., Lang, V., et al., Effects of pigment epithelium-derived factor on traumatic brain injury, Restor. Neurol. Neurosci., 2015, vol. 33, pp. 8193. https://doi.org/10.3233/RNN-140417

Ucar, D., Cogle, C.R., Zucali, J.R., et al., Aldehyde dehydrogenase activity as a functional marker for lung cancer, Chem. -Biol. Interact., 2009, vol. 178, nos. 13, pp. 4855. https://doi.org/10.1016/j.cbi.2008.09.029

Wang, K., Wu, X., Wang, J., et al., Cancer stem cell theory: therapeutic implications for nanomedicine, Int. J. Nanomed., 2013, vol. 8, pp. 899908. https://doi.org/10.2147/IJN.S38641

Wang, Q., Zhang, Z., Ding, T., et al., Mesenchymal stem cells overexpressing PEDF decrease the angiogenesis of gliomas, Biosci. Rep., 2013, vol. 33, art. ID e00019. https://doi.org/10.1042/BSR20110124

Xu, Y., Hu, J., Zhu, Q., et al., Co-detection of ALDH1A1, ABCG2, ALCAM and CD133 in three A549 subpopulations at the single cell level by one-step digital RT-PCR, Integr. Biol., 2018, vol. 10, no. 6, pp. 364369. https://doi.org/10.1039/c8ib00042e

Zhang, L., Chen, J., Ke, Y., et al., Expression of pigment epithelial derived factor is reduced in non-small cell lung cancer and is linked to clinical outcome, Int. J. Mol. Med., 2006, vol. 17, no. 5, pp. 937944.

Zhou, C., Chen, X., Zeng, W., et al., Propranolol induced G0/G1/S phase arrest and apoptosis in melanoma cells via AKT/MAPK pathway, Oncotarget, 2016, vol. 7, pp. 6831468327. https://doi.org/10.18632/oncotarget.11599

Zhou, D., Zhang, M., Xu, P., et al., Expression of pigment epithelium-derived factor is associated with a good prognosis and is correlated with epithelial-mesenchymal transition-related genes in infiltrating ductal breast carcinoma, Oncol. Lett., 2016, vol. 11, pp. 116124. https://doi.org/10.3892/ol.2015.3880

Copyright© ICBGE 2002-2023 Coded & Designed by Volodymyr Duplij Modified 31.01.23