Investigation of Tenascin-C Effects on Thrombospondin 1 in Highly Invasive Breast Cancer Cell Lines

Ali Saleh Alharth^1, , Musaad Abdullah Alsuliman², Waleed Ahmed Alyami², Abobaker Alshamarni², Zyad M Alsulaiman³ and Abdulaziz M Alsulaiman⁴

¹Regional Laboratory, Ministry of Health, Najran, Saudi Arabia

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

³Prince Sultan Military Medical City, Riyadh, Saudi Arabia

⁴Almaarefa University, Riyadh, Saudi Arabia

Cite this paper:
Ali Saleh Alharth, Musaad Abdullah Alsuliman, Waleed Ahmed Alyami, Abobaker Alshamarni, Zyad M Alsulaiman and Abdulaziz M Alsulaiman. Investigation of Tenascin-C Effects on Thrombospondin 1 in Highly Invasive Breast Cancer Cell Lines. American Journal of Medical and Biological Research. 2024; 12(2):81-84. doi: 10.12691/ajmbr-12-2-7

Abstract

Breast cancer is the most diagnosed cancer among women worldwide. Tenascin-C (TNC) is a high glycoprotein which has been shown to be over-expressed in the breast cancer stroma and promotes cancer progression. Thrombospondin 1 (TSP-1) is an adhesive which has been shown to play roles in platelet aggregation, , and . The aim of this study was to investigate the effects of TNC knockdown in TSP-1 expression in highly invasive breast cancer cell lines. Small interfering RNA (siRNA) targeting total TNC and high molecular TNC isoforms (TNC-14 and TNC-14-AD1) were transfected into the highly invasive MDA-MB-231 breast cancer cell line. The alterations caused by TNC knockdown on TSP-1 were analysed at protein level by Western blot using conditioned media. The expression of TSP-1 was significantly up-regulated as a result of TNC down-regulation. In conclusion, TNC knockdown significantly increases TSP-1 expression, confirming their importance in tumorigenesis.

Keywords:
TNC TSP-1 siRNA knockdown

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References:

[1]	Ellsworth RE, Decewicz DJ, Shriver CD, Ellsworth DL. 2010, "Breast Cancer in the Personal Genomics Era", Curr Genomics, vol. 3, no. 3, pp. 146-61.
[2]	Chiquet-Ehrismann, R. & Chiquet, M. 2003, "Tenascins: regulation and putative functions during pathological stress", Journal of Pathology, vol. 200, no. 4, pp. 488-499.
[3]	Alharth, A. S., & Alyami, W. A. (2015). Tenascin-C (TNC) romotes Breast Cancer Cell Invasion and Proliferation: Functional Effects of TNC Knockdown in Highly Invasive Breast Cancer Cell ines. American Journal of Medical and Biological Research, 3(2), 55-61.
[4]	Alharth, Ali S., and Sherien M. El-Daly. "Effects of Tenascin-C (TNC) Knockdown on Global Genes Expression."American Journal of Medical and Biological Research 3.2 (2015): 62-67.
[5]	Chen H, Herndon ME, Lawler J. The cell biology of thrombospondin-1. Matrix Biol. 2000; 19:597-614.
[6]	Naumov GN, Bender E, Zurakowski D, Kang SY, Sampson D, Flynn E, Watnick RS, Straume O, Akslen LA, Folkman J, Almog N. A model of human tumor dormancy: an angiogenic switch from the nonangiogenic phenotype. J Natl Cancer Inst. 2006; 98: 316-325.
[7]	Volpert OV, Pili R, Sikder HA, Nelius T, Zaichuk T, Morris C, Shiflett CB, Devlin MK, Conant K, Alani RM. Id1 regulates angiogenesis through transcriptional repression of thrombospondin-1. Cancer Cell. 2002; 2: 473-483.
[8]	Brown LF, Guidi AJ, Schnitt SJ, Van De Water L, Iruela-Arispe ML, Yeo TK, Tognazzi K, Dvorak HF. Vascular stroma formation in carcinoma in situ, invasive carcinoma, and metastatic carcinoma of the breast. Clin Cancer Res. 1999; 5: 1041-1056.
[9]	Shaked Y, Bertolini F, Man S, Rogers MS, Cervi D, Foutz T, Rawn K, Voskas D, Dumont DJ, Ben-David Y, Lawler J, Henkin J, Huber J, Hicklin DJ, D'Amato RJ, Kerbel RS. Genetic heterogeneity of the vasculogenic phenotype parallels angiogenesis; Implications for cellular surrogate marker analysis of antiangiogenesis. Cancer Cell. 2005; 7: 101-111.
[10]	Rafii DC, Psaila B, Butler J, Jin DK, Lyden D. Regulation of vasculogenesis by platelet-mediated recruitment of bone marrow derived cells. Arterioscler Thromb Vasc Biol. 2008; 28: 217-222.
[11]	Ruiz, C., Huang, W.T., Hegi, M.E., Lange, K., Hamou, M.F., Fluri, E., Oakeley, E.J., Chiquet-Ehrismann, R. & Orend, G. 2004, "Dilfferential gene expression analysis reveals activation of growth promoting signaling pathways by tenascin-C", Cancer research, vol. 64, no. 20, pp. 7377-7385.
[12]	Byrne, G.J., Hayden, K.E., McDowell, G., Lang, H., Kirwan, C.C., Tetlow, L., Kumar, S. & Bundred, N.J. 2007, "Angiogenic characteristics of circulating and tumoural thrombospondin-1 in breast cancer", International journal of oncology, vol. 31, no. 5, pp. 1127-1132.
[13]	Hanamura, N., Yoshida, T., Matsumoto, E., Kawarada, Y. & Sakakura, T. 1997, "Expression of fibronectin and tenascin-C mRNA by myofibroblasts, vascular cells and epithelial cells in human colon adenomas and carcinomas", International Journal of Cancer, vol. 73, no. 1, pp. 10-15.
[14]	Fontana A, Filleur S, Guglielmi J, Frappart L, Bruno-Bossio G, Boissier S, Cabon F, Clézardin P, 2005, "Human breast tumors override the antiangiogenic effect of stromal thrombospondin-1 in vivo", Int J Cancer. 2005 Sep 20; 116(5):686-91.
[15]	Ioachim, E., Damala, K., Tsanou, E., Briasoulis, E., Papadiotis, E., Mitselou, A., Charhanti, A., Doukas, M., Lampri, L. & Arvanitis, D.L. 2012, "Thrombospondin-1 expression in breast cancer: prognostic significance and association with p53 alterations, tumour angiogenesis and extracellular matrix components", Histology and histopathology, vol. 27, no. 2, pp. 209-216.
[16]	John, A.S., Rothman, V.L. & Tuszynski, G.P. 2010, "Thrombospondin-1 (TSP-1) Stimulates Expression of Integrin alpha6 in Human Breast Carcinoma Cells: A Downstream Modulator of TSP-1-Induced Cellular Adhesion.", Journal of oncology, vol. 2010, pp. 645376-645376.
[17]	Canfield, A. & SCHOR, A. 1995, "Evidence that Tenascin and Thrombospondin-1 Modulate Sprouting of Endothelial-Cells", Journal of cell science, vol. 108, pp. 797-809.
[18]	Suh, E.J., Kabir, M.H., Kang, U., Lee, J.W., Yu, J., Noh, D. & Lee, C. 2012, "Comparative profiling of plasma proteome from breast cancer patients reveals thrombospondin-1 and BRWD3 as serological biomarkers", Experimental and Molecular Medicine, vol. 44, no. 1, pp. 36-44.