American Journal of Medical and Biological Research
ISSN (Print): 2328-4080 ISSN (Online): 2328-4099 Website: http://www.sciepub.com/journal/ajmbr Editor-in-chief: Apply for this position
Open Access
Journal Browser
Go
American Journal of Medical and Biological Research. 2015, 3(2), 55-61
DOI: 10.12691/ajmbr-3-2-2
Open AccessArticle

Tenascin-C (TNC) Promotes Breast Cancer Cell Invasion and Proliferation: Functional Effects of TNC Knockdown in Highly Invasive Breast Cancer Cell Lines

Ali S Alharth1, , Musaad A Alsulaiman1 and Waleed A Alyami2

1Department of Public Health, Ministry of Health, Riyadh, Saudi Arabia

2General Health Affairs, Ministry of Health, Riyadh, Saudi Arabia

Pub. Date: April 21, 2015

Cite this paper:
Ali S Alharth, Musaad A Alsulaiman and Waleed A Alyami. Tenascin-C (TNC) Promotes Breast Cancer Cell Invasion and Proliferation: Functional Effects of TNC Knockdown in Highly Invasive Breast Cancer Cell Lines. American Journal of Medical and Biological Research. 2015; 3(2):55-61. doi: 10.12691/ajmbr-3-2-2

Abstract

The tumour microenvironment plays a crucial role in the development of breast cancer. Tenascin-C (TNC), a matricellular protein and its high molecular weight (MW) isoforms have been shown to be over-expressed in the stroma of breast cancers and are associated with poor prognosis. The aim of this study was to investigate the effects of TNC knockdown in TNC expressing invasive breast cancer cell lines on cancer cell behaviour. Small interfering RNA (siRNA) targeting different exons in TNC (24, 14 and 14-AD1) were designed, synthesised and transfected into the highly invasive MDA-MB-231 breast cancer cell line. The phenotypic alterations caused by TNC knockdown were analysed by Two Dimension (2D) invasion assays and proliferation assays using the mitotic marker Phispho-Histone H3 (pHH3). The siRNA targeted cells showed significant down-regulation of both total TNC (p <0.001) and high MW isoforms (p <0.001) in MDA-MB-231 cells. Moreover, knockdown of total TNC and high MW TNC isoforms significantly decreased both cell invasion (total TNC p<0.001 and TNC-14 p <0.001) and proliferation (total TNC p <0.001 and TNC-AD1 p <0.05). In conclusion, TNC knockdown significantly decreases proliferation and invasion in breast cancer cell lines, confirming its importance in breast cancer progression.

Keywords:
TNC siRNA knockdown

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]  ZiOi, Tao, Shi Aimin, Lu Cuntao, Song Tao, Zhao Jing. 2014 “Breast Cancer: Epidemiology and Etiology”, Cell biochemistry and biophysics.
 
[2]  Orend G, Saupe F, Schwenzer A, Midwood K. “The extracellular matrix and cancer: regulation of tumor cell biology by tenascin-C”. iConcept Press 2014. p. 1-139.
 
[3]  Pickup MW, Mouw JK, Weaver VM. The extracellular matrix modulates the hallmarks of cancer. EMBO Rep 2014; 15(12):1243-53; PMID:25381661
 
[4]  Jones, P.L. 2001, “Extracellular matrix and tenascin-C in pathogenesis of breast cancer”, Lancet, vol. 357, no. 9273, pp. 1992-1994.
 
[5]  Ioachim E, Charchanti A, Briasoulis E, Karavasilis V, Tsanou H, Arvanitis DL, Agnantis NJ, Pavlidis N: 2002,” Immunohistochemical expression of extracellular matrix components tenascin, fibronectin, collagen type IV and laminin in breast cancer: their prognostic value and role in tumour invasion and progression”, Eur J Cancer, vol. 38, pp. 2362-2370.
 
[6]  Midwood, K.S. & Orend, G. 2009, “The role of tenascin-C in tissue injury and tumorigenesis.”, Journal of cell communication and signaling, vol. 3, no. 3-4, pp. 287-310.
 
[7]  Joester, A. & Faissner, A. 2001, “The structure and function of tenascins in the nervous system”, Matrix Biology, vol. 20, no. 1, pp. 13-22.
 
[8]  Orend, G. 2005, “Potential oncogenic action of tenascin-C in tumorigenesis”, International Journal of Biochemistry & Cell Biology, vol. 37, no. 5, pp. 1066-1083.
 
[9]  Jahkola, T., Toivonen, T., Nordling, S., von Smitten, K. & Virtanen, I. 1998a, “Expression of tenascin-C in intraductal carcinoma of human breast: Relationship to invasion”, European journal of cancer, vol. 34, no. 11, pp. 1687-1692.
 
[10]  Ishihara, A., Yoshida, T., Tamaki, H. & Sakakura, T. 1995, “Tenascin expression in cancer cells and stroma of human breast cancer and its prognostic significance”, Clinical Cancer Research, vol. 1, no. 9, pp. 1035-1041.
 
[11]  Chiquet-Ehrismann, R. & Chiquet, M. 2003, “Tenascins: regulation and putative functions during pathological stress”, Journal of Pathology, vol. 200, no. 4, pp. 488-499.
 
[12]  Adams, M., Jones, J.L., Walker, R.A., Pringle, J.H. & Bell, S.C. 2002, “Changes in tenascin-C isoform expression in invasive and preinvasive breast disease”, Cancer research, vol. 62, no. 11, pp. 3289.
 
[13]  Hancox, R.A., Allen, M.D., Holliday, D.L., Edwards, D.R., Pennington, C.J., Guttery, D.S., Shaw, J.A., Walker, R.A., Pringle, J.H. & Jones, J.L. 2009, “Tumour-associated tenascin-C isoforms promote breast cancer cell invasion and growth by matrix metalloproteinase-dependent and independent mechanisms”, Breast Cancer Research, vol. 11, no. 2.
 
[14]  Guttery, D.S., Hancox, R.A., Mulligan, K.T., Hughes, S., Lambe, S.M., Pringle, J.H., Walker, R.A., Jones, J.L. & Shaw, J.A. 2010a, “Association of invasion-promoting tenascin-C additional domains with breast cancers in young women”, Breast Cancer Research, vol. 12, no. 4, pp. R57.
 
[15]  Tavazoie, S.F., Alarcon, C., Oskarsson, T., Padua, D., Wang, Q., Bos, P.D., Gerald, W.L. & Massague, J. 2008, “Endogenous human microRNAs that suppress breast cancer metastasis”, Nature, vol. 451, no. 7175, pp. 147-U3.
 
[16]  Zukiel, R., Nowak, S., Wyszko, E., Rolle, K., Gawronska, I., Barciszewska, M.Z. & Barciszewski, J. 2006, “Suppression of human brain tumor with interference RNA specific for tenascin-C”, Cancer Biology & Therapy, vol. 5, no. 8, pp. 1002-1007.
 
[17]  Hirata, E., Arakawa, Y., Shirahata, M., Yamaguchi, M., Kishi, Y., Okada, T., Takahashi, J.A., Matsuda, M. & Hashimoto, N. 2009, “Endogenous tenascin-C enhances glioblastoma invasion with reactive change of surrounding brain tissue”, Cancer Science, vol. 100, no. 8, pp. 1451-1459.
 
[18]  Fukunaga-Kalabis, M., Martinez, G., Nguyen, T.K., Kim, D., Santiago-Walker, A., Roesch, A. & Herlyn, M. 2010, “Tenascin-C promotes melanoma progression by maintaining the ABCB5-positive side population”, Oncogene, vol. 29, no. 46, pp. 6115-6124.
 
[19]  Veras, E., Malpica, A., Deavers, M.T. & Silva, E.G. 2009, “Mitosis-specific Marker Phospho-histone H3 in the Assessment of Mitotic Index in Uterine Smooth Muscle Tumors: A Pilot Study”, International Journal of Gynecological Pathology, vol. 28, no. 4, pp. 316-321.
 
[20]  Tuominen, V.J., Ruotoistenmaki, S., Viitanen, A., Jumppanen, M. & Isola, J. 2010, “ImmunoRatio: a publicly available web application for quantitative image analysis of estrogen receptor (ER), progesterone receptor (PR), and Ki-67”, Breast Cancer Research, vol. 12, no. 4, pp. R56.
 
[21]  Tsunoda, T., Inada, H., Kalembeyi, I., Imanaka-Yoshida, K., Sakakibara, M., Okada, R., Katsuta, K., Sakakura, T., Majima, Y. & Yoshida, T. 2003, “Involvement of large tenascin-C splice variants in breast cancer progression”, American Journal of Pathology, vol. 162, no. 6, pp. 1857-1867.
 
[22]  Viale, G.L., Castellani, P., Dorcaratto, A., Pau, A., Sehrbundt, E., Siri, A., Biro, A. & Zardi, L. 2002, “Occurrence of a glioblastoma-associated tenascin-C isoform in cerebral cavernomas and neighboring vessels”, Neurosurgery, vol. 50, no. 4, pp. 838-842.
 
[23]  Sriramarao, P. & Bourdon, M.A. 1993a, “A Novel Tenascin Type-Iii Repeat is Part of a Complex of Tenascin Messenger-Rna Alternative Splices”, Nucleic acids research, vol. 21, no. 1, pp. 163-168.
 
[24]  Mighell, A.J., Thompson, J., Hume, W.J., Markham, A.F. & Robinson, P.A. 1997, “Human tenascin-C: Identification of a novel type III repeat in oral cancer and of novel splice variants in normal, malignant and reactive oral mucosae”, International Journal of Cancer, vol. 72, no. 2, pp. 236-240.
 
[25]  Derr, L.B., Chiquet-Ehrismann, R., GandourEdwards, R., Spence, J. & Tucker, R.P. 1997, “The expression of tenascin-C with the AD1 variable repeat in embryonic tissues, cell lines and tumors in various vertebrate species”, Differentiation, vol. 62, no. 2, pp. 71-82.