N-Cadherin as An Important Marker in Colorectal Cancer: An investigation of b-Catenin and Cadherin Expressions of SW-480 and HCT-116 Cell Lines

Winarko Luminturahardjo, Djoko Wahono Soeatmadji, Karyono Mintaroem, Pudji Rahajoe, Ferry Sandra

Abstract


BACKGROUND: The absence of potential biomarkers to detect the metastatic process at an early stage will consequently delay colorectal cancer (CRC) treatment. Some biomarkers including β-Catenin, E-Cadherin and N-Cadherin have been suggested as potential markers. However, there were opposite reports regarding expressions of these markers. Therefore, current study was conducted using CRC cell lines for early stage (SW-480 cells) and late stage (HCT-116 cells) of CRC.

METHODS: SW-480 and HCT-116 cells were cultured and seeded on coverslip glasses for immunofluorescence staining to detect β-Catenin, E-cadherin, and N-cadherin. Expressions of β-Catenin, E-cadherin, and N-cadherin were observed and documented under a fluorescent microscope and analyzed with Image J software. Measured results were then statistically analyzed.

RESULTS: All β-catenin, E-Cadherin and N-Cadherin expressions were observed in SW-480 and HCT-116 cells. β-catenin MFI averages of SW-480 (47.157±3.479) and HCT-116 (47.240±4.107) cells were similar. E-Cadherin MFI average of SW-480 cells (45.104±4.107) was higher than the one of HCT-116 cells (40.191±3.702). N-Cadherin MFI average of HCT-116 cells (43.702±8.219) was significantly higher (p=0.009) than the one of SW-480 cells (72.506±5.297).

CONCLUSION: Taken together, N-Cadherin could be suggested as an important metastasis marker in CRC since the N-Cadherin expression was significantly higher in HCT-116 cells as the late-stage CRC model than SW-480 as the early-stage of CRC model. Further research is still needed by comparing several biomarkers from various clinical samples at all clinical stages of CRC.

KEYWORDS: CRC, β-Catenin, E-Cadherin, N-Cadherin, Metastasis, Biomarker


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References


Wanandi SI, Lestari DR, Hilbertina N, Siregar NC, Jusman SW, Abdullah M. Secretomes of primary cancer-associated fibroblasts upregulate the expression of stemness markers in HT-29 human colorectal carcinoma cells. Indones Biomed J. 2020; 12: 333-9, CrossRef.

Stanczak A, Stec R, Bodnar L, Olszewski W, Cichowicz M, Kozlowski W, Szczylik C, et al. Prognostic significance of Wnt-1, β-catenin and E-cadherin expression in advanced colorectal carcinoma. Pathol Oncol Res. 2011; 17: 955-63, CrossRef.

Ahmad A, Stromberg VH. Expression of β-catenin and E-cadherin, their clinical significance and association with complexity and index of colon carcinoma. Adv Genet Eng. 2016; 5: 1-10, CrossRef.

Palaghia M, Mihai C, Lozneanu L, Ciobanu D, Trofin AM. E-cadherin expression in primary colorectal cancer and metastatic lymph nodes. Rom J Morphol Embryol. 2016; 57: 205-9, PMID.

Tedjasaputra TR, Hatta M, Massi MN, Natzir R, Patellongi I, Simadibrata M, et al. Risk assessment in hereditary colorectal cancer family by using APC and MSH2 mRNA gene expression and bayesian analysis. Indones Biomed J. 2020; 12: 368-75, CrossRef.

Kamiyama H, Noda H, Konishi F, Rikiyama T. Molecular biomarkers for the detection of metastatic colorectal cancer cells. World J Gastroenterol. 2014; 20: 8928-38, CrossRef.

Lips DJ, Koebrugge B, Jan Liefers G, van de Linden JC, Smit VT, Pruijt HF, et al. The influence of micrometastases on prognosis and survival in stage I-II colon cancer patients: the Enroute Study. BMC Surgery. 201; 11: [n.p.], CrossRef.

Yamamoto H, Murata K, Fukunaga M, Ohnishi T, Noura S, Miyake Y, et al. Micrometastatis volume in lymph nodes determines disease recurrence rate of stage II colorectal cancer: a prospective multicenter trial. Clin Cancer Res. 2016; 22: 3201-8, CrossRef.

Bilchick AJ, Nora DT, Saha S, Turner R, Wiese D, Kuo C, et al. The use of molecular profiling of early colorectal cancer to predict micrometastases. Arch Surg. 2002; 137: 1377-83, CrossRef.

Chen J, Xie ZR, Wu Y. Computational modeling of the interplay between cadherin-mediated cell adhesion and wnt signaling pathway. PLoS ONE. 2014; 9: 1-12, CrossRef.

Wheelock MJ, Shintani Y, Maeda M, Fukumoto Y, Johnson KR. Cadherin switching. J Cell Sci. 2007; 121: 727-35, CrossRef.

Shang S, Hua F, Hu ZW. The regulation of β-catenin activity and function in cancer: therapeutic opportunities. Oncotarget. 2017; 8: 33972-89, CrossRef.

Menezes ME. The Wnt/β-catenin signaling pathway in epithelial mesenchymal transition. Post Doc Journal. 2014; 2: 1-9, CrossRef.

Heuberger J, Birchmeier W. Interplay of cadherin-mediated cell adhesion and canonical wnt signaling. Cold Spring Harb Percpect Biol. 2010; 2: a002915, CrossRef.

Mrozik KM, Blaschuk OW, Cheong CM, Zannettino ACW, Vandyke K. N-cadherin in cancer metastases, its emerging role in haematological malignancies and potential as a therapeutic target in cancer. BMC Cancer. 2018; 18: 939, CrossRef.

Loh C, Chai JY, Tang TF, Wong WF, Sethi G, Shanmugan MK, et al. The E-cadherin and N-cadherin switch in epithelial to mesenchymal transition: signaling, therapeutic implications, and challenges. Cells. 2019; 8: 1-33, CrossRef.

Bhattacharya I, Barman N, Maiti M, Sarkar R. Assesment of beta-catenin expression by immunohistochemistry in colorectal neoplasm and its role as an additional prognostic marker in colorectal adenocarcinoma. Med Pharm Rep. 2019; 9: 246-52, CrossRef.

Yuan S, Tao F, Zhang X, Zhang Y, Sun X, Wu D. Role of Wnt/β-catenin signaling in the chemoresistance modulation of colorectal cancer. Biomed Res Int. 2020; 2020: 9390878, CrossRef.

Li S, Huang M, Liu Q, Wang D, Wu R, Zhang X, et al. Serum expression of β-catenin is a potential detection marker in patients with colorectal cancer. Dis Markers. 2019; 2019: 5070524, CrossRef.

Daulagala A, Bridges MC, Kourtidis A. E-cadherin beyond structure: a signaling hub in colon homeostasis and disease. Int J Mol Sci. 2019; 20: 2756, CrossRef.

Liang X, Xu X, Wang F, Chen X, Li N, Wang C, et al. E-cadherin knockdown increases β-catenin reducing colorectal cancer chemosensitivity only in three-dimensional cultures. Int J Oncol. 2015; 47: 1517-27, CrossRef.

He X, Chen Z, Jia M, Zhao X. Downregulated E-cadherin expression indicates worse prognosis in asian patients with colorectal cancer: evidence from meta-analysis. PLoS ONE. 2013; 8: e70858, CrossRef.

Kim SA, Inamura K, Yamauchi M, Nishihara R, Mima K, Sukawa Y, et al. Loss of CDH1 (E-cadherin) expression is associated with infiltrative tumor growth and lymph node metastasis. Be J Cancer. 2016; 114: 199-206, CrossRef.

Yan X, Yan L, Liu S, Shan Z, Tian Y. N-cadherin, a novel prognostic biomarker, drives malignant progression of colorectal cancer. Mol Med Rep. 2015; 12: 2999-3006, CrossRef.

Ye Z, Zhou M, Tian B, Wu B, Li Z. Expression of IncRNA-CCAT1, E-cadherin and N-cadherin in colorectal cancer and its significance. Int J Clin Exp Med. 2015; 8: 3707-15, PMID.




DOI: https://doi.org/10.18585/inabj.v13i3.1562

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