CD44 promotes cell proliferation in non-small cell lung cancer

Hu,Bo; Ma,Yuanyuan; Yang,Yue; Zhang,Lijian; Han,Haibo; Chen,Jinfeng

doi:10.3892/ol.2018.8051

CD44 promotes cell proliferation in non-small cell lung cancer

Authors:
- Bo Hu
- Yuanyuan Ma
- Yue Yang
- Lijian Zhang
- Haibo Han
- Jinfeng Chen
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Affiliations: Department of Thoracic Surgery II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China, Department of Biobank, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China
Published online on: February 14, 2018 https://doi.org/10.3892/ol.2018.8051
Pages: 5627-5633
Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cluster of differentiation 44 (CD44), a marker for cancer stem cells, has been reported to be associated with poor prognosis in non‑small cell lung cancer (NSCLC), but its involvement in tumor growth has not fully been elucidated. The present study explored the associations between CD44 expression and clinicopathological features using immunohistochemistry in 94 NSCLC cases, as well as proliferation in cells with aberrant expression of this protein. Overexpression of CD44 was achieved by transfecting H1299 cells with CD44 expression vectors, and inhibition of CD44 expression was performed by transfecting small interfering RNAs into A549 cells. Cell proliferation was measured using Cell Counting Kit‑8 assays and flat plate colony formation assay was performed to confirm the cellular anchorage growth in vitro. In total, 64 (68.1%) of the 94 NSCLC cases stained positive for CD44 expression. High expression of CD44 was associated with advanced T stage in NSCLC. Overexpression of CD44 in H1299 cells promoted cell proliferation and colony formation in vitro. Meanwhile, knockdown of CD44 expression in A549 cells suppressed cell proliferation and colony formation in vitro. High expression of CD44 may promote NSCLC progression by increasing cancer cell proliferation; therefore, it may serve as a potential biomarker for diagnosis or target therapy.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI
2	Graham MV, Purdy JA, Emami B, Harms W, Bosch W, Lockett MA and Perez CA: Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer (NSCLC). Int J Radiat Oncol Biol Phys. 45:323–329. 1999. View Article : Google Scholar : PubMed/NCBI
3	Sterlacci W, Stockinger R, Schmid T, Bodner J, Hilbe W, Waldthaler C, Oberaigner W, Tzankov A and Fiegl M: The elderly patient with surgically resected non-small cell lung cancer-a distinct situation? Exp Gerontol. 47:237–242. 2012. View Article : Google Scholar : PubMed/NCBI
4	Prochazka L, Tesarik R and Turanek J: Regulation of alternative splicing of CD44 in cancer. Cell Signal. 26:2234–2239. 2014. View Article : Google Scholar : PubMed/NCBI
5	Naor D, Sionov RV and Ish-Shalom D: CD44: Structure, function, and association with the malignant process. Adv Cancer Res. 71:241–319. 1997. View Article : Google Scholar : PubMed/NCBI
6	Xu H, Tian Y, Yuan X, Liu Y, Wu H, Liu Q, Wu GS and Wu K: Enrichment of CD44 in basal-type breast cancer correlates with EMT, cancer stem cell gene profile, and prognosis. Onco Targets Ther. 9:431–444. 2016.PubMed/NCBI
7	Aso T, Matsuo M, Kiyohara H, Taguchi K, Rikimaru F, Shimokawa M, Segawa Y, Higaki Y, Umeno H, Nakashima T and Masuda M: Induction of CD44 variant 9-expressing cancer stem cells might attenuate the efficacy of chemoradioselection and worsens the prognosis of patients with advanced head and neck cancer. PLoS One. 10:e01165962015. View Article : Google Scholar : PubMed/NCBI
8	Fang M, Wu J, Lai X, Ai H, Tao Y, Zhu B and Huang L: CD44 and CD44v6 are correlated with gastric cancer progression and poor patient prognosis: Evidence from 42 studies. Cell Physiol Biochem. 40:567–578. 2016. View Article : Google Scholar : PubMed/NCBI
9	Sosulski A, Horn H, Zhang L, Coletti C, Vathipadiekal V, Castro CM, Birrer MJ, Nagano O, Saya H, Lage K, et al: CD44 splice variant v8-10 as a marker of serous ovarian cancer prognosis. PLoS One. 11:e01565952016. View Article : Google Scholar : PubMed/NCBI
10	Yikilmaz TN, Dirim A, Ayva ES, Ozdemir H and Ozkardes H: Clinical use of tumor markers for the detection and prognosis of bladder carcinoma: A comparison of CD44, cytokeratin 20 and survivin. Urol J. 13:2677–2683. 2016.PubMed/NCBI
11	Jiang H, Zhao W and Shao W: Prognostic value of CD44 and CD44v6 expression in patients with non-small cell lung cancer: Meta-analysis. Tumour Biol. 35:7383–7389. 2014. View Article : Google Scholar : PubMed/NCBI
12	Zhao S, He JL, Qiu ZX, Chen NY, Luo Z, Chen BJ and Li WM: Prognostic value of CD44 variant exon 6 expression in non-small cell lung cancer: A meta-analysis. Asian Pac J Cancer Prev. 15:6761–6766. 2014. View Article : Google Scholar : PubMed/NCBI
13	Situ D, Long H, Lin P, Zhu Z, Wang J, Zhang X, Xie Z and Rong T: Expression and prognostic relevance of CD44v6 in stage I non-small cell lung carcinoma. J Cancer Res Clin Oncol. 136:1213–1219. 2010. View Article : Google Scholar : PubMed/NCBI
14	Shinohara S, Hanagiri T, Taira A, Takenaka M, Oka S, Chikaishi Y, Uramoto H, So T, Yamada S and Tanaka F: Immunohistochemical expression and serum levels of CD44 as prognostic indicators in patients with non-small cell lung cancer. Oncology. 90:327–338. 2016. View Article : Google Scholar : PubMed/NCBI
15	Li G, Gao Y, Cui Y, Zhang T, Cui R, Jiang Y and Shi J: Overexpression of CD44 is associated with the occurrence and migration of non-small cell lung cancer. Mol Med Rep. 14:3159–3167. 2016. View Article : Google Scholar : PubMed/NCBI
16	Su J, Wu S, Wu H, Li L and Guo T: CD44 is functionally crucial for driving lung cancer stem cells metastasis through Wnt/β-catenin-FoxM1-twist signaling. Mol Carcinog. 55:1962–1973. 2016. View Article : Google Scholar : PubMed/NCBI
17	Leung EL, Fiscus RR, Tung JW, Tin VP, Cheng LC, Sihoe AD, Fink LM, Ma Y and Wong MP: Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties. PLoS One. 5:e140622010. View Article : Google Scholar : PubMed/NCBI
18	Roudi R, Madjd Z, Korourian A, Mehrazma M, Molanae S, Sabet MN and Shariftabrizi A: Clinical significance of putative cancer stem cell marker CD44 in different histological subtypes of lung cancer. Cancer Biomark. 14:457–467. 2014. View Article : Google Scholar : PubMed/NCBI
19	Liu J, Xiao Z, Wong SK, Tin VP, Ho KY, Wang J, Sham MH and Wong MP: Lung cancer tumorigenicity and drug resistance are maintained through ALDH(hi)CD44 (hi) tumor initiating cells. Oncotarget. 4:1698–1711. 2013. View Article : Google Scholar : PubMed/NCBI
20	Chen J, Xie F, Zhang L and Jiang WG: iASPP is over-expressed in human non-small cell lung cancer and regulates the proliferation of lung cancer cells through a p53 associated pathway. BMC Cancer. 10:6942010. View Article : Google Scholar : PubMed/NCBI
21	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
22	Sui X, Jiang W, Chen H, Yang F, Wang J and Wang Q: Validation of the stage groupings in the eighth edition of the TNM classification for lung cancer. J Thorac Oncol. 12:1679–1686. 2017. View Article : Google Scholar : PubMed/NCBI
23	Luo Z, Wu RR, Lv L, Li P, Zhang LY, Hao QL and Li W: Prognostic value of CD44 expression in non-small cell lung cancer: A systematic review. Int J Clin Exp Pathol. 7:3632–3646. 2014.PubMed/NCBI
24	Liu Y, Qing H, Su X, Wang C, Li Z and Liu S: Association of CD44 gene polymorphism with survival of NSCLC and risk of bone metastasis. Med Sci Monit. 21:2694–2700. 2015. View Article : Google Scholar : PubMed/NCBI
25	Nguyen VN, Mirejovský T, Melinová L and Mandys V: CD44 and its v6 spliced variant in lung carcinomas: Relation to NCAM, CEA, EMA and UP1 and prognostic significance. Neoplasma. 47:400–408. 2000.PubMed/NCBI
26	Afify AM, Tate S, Durbin-Johnson B, Rocke DM and Konia T: Expression of CD44s and CD44v6 in lung cancer and their correlation with prognostic factors. Int J Biol Markers. 26:50–57. 2011. View Article : Google Scholar : PubMed/NCBI
27	Jordan AR, Racine RR, Hennig MJ and Lokeshwar VB: The role of CD44 in disease pathophysiology and targeted treatment. Front Immunol. 6:1822015. View Article : Google Scholar : PubMed/NCBI