Effects of SPARC and Possible Receptors on Colon Cancer Cell Line

Duygu MISIRLI, (Sağlık Bilimleri Üniversitesi, Hamidiye Eczacılık Fakültesi, Biyokimya Anabilim Dalı, İstanbul, Türkiye)
Özlem BİNGÖL ÖZAKPINAR, (Marmara Üniversitesi, Eczacılık Fakültesi, Biyokimya Anabilim Dalı, İstanbul, Türkiye)
Turgut ŞEKERLER, (Marmara Üniversitesi, Eczacılık Fakültesi, Biyokimya Anabilim Dalı, İstanbul, Türkiye)
BASAK ARU, (Yeditepe Üniversitesi, Tıp Fakültesi, İmmünoloji Anabilim Dalı, İstanbul, Türkiye)
Gülderen Yanıkkaya Demirel, (Yeditepe Üniversitesi, Tıp Fakültesi, İmmünoloji Anabilim Dalı, İstanbul, Türkiye)
Servet Tunoglu, (İstanbul Üniversitesi, Aziz Sancar Deneysel Tıp Araştırma Enstitüsü, Moleküler Tıp Anabilim Dalı, İstanbul, Türkiye)
Derya OZSAVCİ (Marmara Üniversitesi, Eczacılık Fakültesi, Biyokimya Anabilim Dalı, İstanbul, Türkiye)
Clinical and Experimental Health Sciences
5 1
Yıl: 2023 Cilt: 13 Sayı: 2 Sayfa Aralığı: 316 - 322 Metin Dili: İngilizce DOI: 10.33808/clinexphealthsci.1100770 İndeks Tarihi: 31-07-2023

Effects of SPARC and Possible Receptors on Colon Cancer Cell Line

Öz:
Objective: The aim of this study was to observe the apoptotic/cytotoxic effects of exogenous SPARC on colon cancer cell line HT-29, then to investigate the function of stabilin-1 and integrin αvβ3, which are possible receptors for SPARC in colon cancer cells and to determine the quantitation of their receptor numbers. Methods: Appropriate doses of exogenous SPARC and it’s inhibitor, cilengitide added to HT-29 cell line were determined by xCELLigence Real-Time Cell Analysis system, SPARC-mediated caspase 3 expressions were measured. Using the RT-PCR system, gene expression levels of SPARC, stabilin-1 and integrin αvβ3 receptors (silenced/nonsilenced with cilengitide) were detected then the numbers of receptors per cell were quantitated by flow cytometry. Results: IC50 value of SPARC was determined as 4.57 μg/mL and IC50 value of cilengitide was determined as 50 nM. 5 μg/mL exogenous SPARC caused increased apoptosis in the HT-29 line. Significant increase in gene expression of integrin αvβ3 receptor was observed in the group incubated with 5 μg/mL SPARC, contrarily, the addition of cilengitide decreased gene expressions. The integrin αvβ3 receptor numbers increased approximately 2-fold with SPARC compared to the control. No significant changes were observed in the gene expression and receptor numbers of stabilin-1. Conclusion: Exogenous SPARC was shown to reduce proliferation and induce apoptosis in colon cancer cells. Integrin αvβ3 is thought to be the possible receptor mediating SPARC in colon cancer cells. Quantification of surface receptors per cell, which we think we have done first, can be considered as a marker in the follow-up of anticancer treatments.
Anahtar Kelime: SPARC cilengitide colon cancer stabilin-1 integrin αvβ3

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • [1] Yan Q, Sage EH. SPARC, a matricellular glycoprotein with important biological functions. J Histochem Cytochem 1999; 47(12): 1495-1506. https://doi.org/10.1177/002.215.549904 701201.
  • [2] Sage H, Tupper J, Bramson R. Endothelial cell injury in vitro is associated with increased secretion of an Mr 43,000 glycoprotein ligand. J Cell Physiol 1986; 127(3): 373-387. https://doi.org/10.1002/jcp.104.127.0305.
  • [3] Bradshaw AD, Sage EH. SPARC, a matricellular protein that functions in cellular differentiation and tissue response to injury. J Clin Invest 2001; 107(9): 1049-1054. https://doi. org/10.1172/JCI12939.
  • [4] De Souza Viana L, Affonso JrRJ, Silva SRM, Denadai MVA, Matos D, De Souza CS, Waisberg J. Relationship between the expression of the extracellular matrix genes SPARC, SPP1, FN1, ITGA5 and ITGAV and clinicopathological parameters of tumor progression and colorectal cancer dissemination. Oncology 2013; 84(2): 81-91. doi: 10.1159/000343436.
  • [5] Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61(2): 69-90. doi:10.3322/caac.20107.
  • [6] Yang E, Kang HJ, Koh KH, Rhee H, Kim NK, Kim H. Frequent inactivation of SPARC by promoter hypermethylation in colon cancers. Int J Cancer 2007; 121(3): 567-575. https://doi. org/10.1002/ijc.22706.
  • [7] Kzhyshkowska J, Gratchev A, Schmuttermaier C, Brundiers H, Krusell L, Mamidi S, Zhang J, Workman G, Sage EH, Anderle C, Sedlmayr P, Goerdt, S. Alternatively activated macrophages regulate extracellular levels of the hormone placental lactogen via receptor-mediated uptake and transcytosis. J Immunol 2008; 180(5): 3028-3037. doi: 10.4049/jimmunol.180.5.3028.
  • [8] Mas-Moruno C, Fraioli R, Rechenmacher F, Neubauer S, Kapp TG, Kessler H. αvβ3 – or α5β1-Integrin-Selective Peptidomimetics for Surface Coating. Angew Chem Int Ed Engl 2016; 55(25): 7048-7067. DOI: 10.1002/anie.201509782.
  • [9] Zoppi N, Chiarelli N, Ritelli M, Colombi M. Multifaced Roles of the αvβ3 Integrin in Ehlers-Danlos and Arterial Tortuosity Syndromes’ Dermal Fibroblasts. Int J Mol Sci 2018; 19(4), 982. doi:10.3390/ijms19040982.
  • [10] Dejana E, Raiteri M, Resnati M, Lampugnani MG. Endothelial integrins and their role in maintaining the integrity of the vessel wall. Kidney Int 1993; 43(1): 61-65. https://doi.org/10.1038/ ki.1993.11.
  • [11] Serini G, Valdembri D, Bussolino F, Integrins and angiogenesis: a sticky business. Exp Cell Res 2006; 312(5): 651-658. https:// doi.org/10.1016/j.yexcr.2005.10.020.
  • [12] Mas-Moruno C, Rechenmacher F, Kessler H. Cilengitide: the first anti-angiogenic small molecule drug candidate design, synthesis and clinical evaluation. Anticancer Agents Med Chem 2010; 10(10): 753-768. doi: 10.2174/187.152.010794728639.
  • [13] Hynes RO, Integrins: bidirectional, allosteric signaling machines. Cell 2002; 110(6): 673-687. https://doi.org/10.1016/S0092- 8674(02)00971-6.
  • [14] Haubner R, Finsinger D, Kessler H. Stereoisomeric peptide libraries and peptidomimetics for designing selective inhibitors of the αvβ3 integrin for a new cancer therapy. Angew Chem Int Ed Engl 1997; 36(13-14): 1374-1389. https://doi.org/10.1002/ anie.199713741.
  • [15] Heckmann D, Kessler H, Design and chemical synthesis of integrin ligands. Methods Enzymol 2007; 426: 463-503. https://doi.org/10.1016/S0076-6879(07)26020-3.
  • [16] Taga T, Suzuki A, Gonzalez-Gomez I, Gilles FH, Stins M, Shimada H, Barsky L. Weinberg KI, Laug, W. E. αv-Integrin antagonist EMD 121974 induces apoptosis in brain tumor cells growing on vitronectin and tenascin. Int J Cancer 2002; 98(5): 690-697. https://doi.org/10.1002/ijc.10265.
  • [17] Paolillo M, Russo MA, Serra M, Colombo L, Schinelli S. Small molecule integrin antagonists in cancer therapy. Mini Rev Med Chem 2009; 9(12): 1439-1446. https://doi.org/10.2174/138.9 55.709789957404.
  • [18] Kielkopf CL, Bauer W, Urbatsch IL. Bradford Assay for Determining Protein Concentration. Cold Spring Harb Protoc. 2020; 2020(4):102269. doi:10.1101/pdb.prot102269.
  • [19] Yan G, Du Q, Wei X, Miozzi J, Kang C, Wang J, Han X, Pan J, Xie H, Chen J, Zhang W. Application of Real-Time Cell Electronic Analysis System in Modern Pharmaceutical Evaluation and Analysis. Molecules 2018; 23(12): 3280. https://doi. org/10.3390/molecules23123280.
  • [20] Said NA, Najwer I, Socha MJ, Fulton DJ, Mok SC, Motamed, K. SPARC inhibits LPA-mediated mesothelial-ovarian cancer cell crosstalk. Neoplasia 2007; 9(1): 23-35. https://doi. org/10.1593/neo.06658.
  • [21] Shin M, Mizokami A, Kim J, Ofude M, Konaka H, Kadono Y, Kitagawa Y, Miwa S, Kumaki M, Keller ET, Namiki M. Exogenous SPARC suppresses proliferation and migration of prostate cancer by interacting with integrin β1. Prostate 2013; 73(11): 1159-1170. https://doi.org/10.1002/pros.22664.
  • [22] Yiu GK, Chan WY, Ng SW, Chan PS, Cheung KK, Berkowitz RS, Mok SC. SPARC (secreted protein acidic and rich in cysteine) induces apoptosis in ovarian cancer cells. Am J Pathol 2001; 159(2): 609-622. https://doi.org/10.1016/S0002- 9440(10)61732-4.
  • [23] Fenouille N, Puissant A, Tichet M, Zimniak G, Abbe P, Mallavialle A, Rocchi S, Ortonne J-P, Deckert M, Ballotti R, Tartare-Deckert S. SPARC functions as an anti-stress factor by inactivating p53 through Akt-mediated MDM2 phosphorylation to promote melanoma cell survival. Oncogene 2011; 30(49): 4887-4900. https://doi.org/10.1038/onc.2011.198.
  • [24] Chen J, Wang M, Xi B, Xue J, He D, Zhang J, Zhao Y. SPARC is a key regulator of proliferation, apoptosis and invasion in human ovarian cancer. PLoS One 2012; 7(8): e42413. https:// doi.org/10.1371/journal.pone.0042413.
  • [25] Chern YJ, Wong JC, Cheng GS, Yu A, Yin Y, Schaeffer DF, Kennecke HF, Morin G, Tai IT. The interaction between SPARC and GRP78 interferes with ER stress signaling and potentiates apoptosis via PERK/eIF2α and IRE1α/XBP-1 in colorectal cancer. Cell Death Dis 2019; 10(7): 1-14. https://doi.org/10.1038/ s41419.019.1687-x.
  • [26] Gerson KD, Shearstone JR, Maddula VK, Seligmann BE, Mercurio AM. Integrin β4 regulates SPARC protein to promote invasion. J Biol Chem 2012; 287(13): 9835-9844. https://doi. org/10.1074/jbc.M111.317727.
  • [27] Girotti MR, Fernández M, López JA, Camafeita E, Fernández EA, Albar JP, Benedetti LG, Valacco MP, Brekken RA, Podhajcer OL, Llera AS. SPARC promotes cathepsin B-mediated melanoma invasiveness through a collagen I/α2β1 integrin axis. J Invest Dermatol 2011; 131(12): 2438-2447. https://doi.org/10.1038/ jid.2011.239.
  • [28] Kzhyshkowska J, Workman G, Cardó-Vila M, Arap W, Pasqualini R, Gratchev A, Krusell L, Goerdt S, Sage EH. Novel function of alternatively activated macrophages: stabilin-1-mediated clearance of SPARC. J Immunol 2006; 176(10): 5825-5832. https://doi.org/10.4049/jimmunol.176.10.5825.
  • [29] Said N, Najwer I, Motamed K. Secreted protein acidic and rich in cysteine (SPARC) inhibits integrin-mediated adhesion and growth factor-dependent survival signaling in ovarian cancer. Am J Pathol 2007; 170(3): 1054-1063. https://doi. org/10.2353/ajpath.2007.060903.
  • [30] Said N, Socha MJ, Olearczyk JJ, Elmarakby AA, Imig JD, Motamed K. Normalization of the ovarian cancer microenvironment by SPARC. Mol Cancer Res 2007; 5(10): 1015-1030. https://doi. org/10.1158/1541-7786.MCR-07-0001.
APA Mısırlı D, Bingöl Özakpınar Ö, şekerler t, ARU B, Yanikkaya Demirel G, Tunoglu S, Ozsavci D (2023). Effects of SPARC and Possible Receptors on Colon Cancer Cell Line. , 316 - 322. 10.33808/clinexphealthsci.1100770
Chicago Mısırlı Duygu,Bingöl Özakpınar Özlem,şekerler turgut,ARU BASAK,Yanikkaya Demirel Gulderen,Tunoglu Servet,Ozsavci Derya Effects of SPARC and Possible Receptors on Colon Cancer Cell Line. (2023): 316 - 322. 10.33808/clinexphealthsci.1100770
MLA Mısırlı Duygu,Bingöl Özakpınar Özlem,şekerler turgut,ARU BASAK,Yanikkaya Demirel Gulderen,Tunoglu Servet,Ozsavci Derya Effects of SPARC and Possible Receptors on Colon Cancer Cell Line. , 2023, ss.316 - 322. 10.33808/clinexphealthsci.1100770
AMA Mısırlı D,Bingöl Özakpınar Ö,şekerler t,ARU B,Yanikkaya Demirel G,Tunoglu S,Ozsavci D Effects of SPARC and Possible Receptors on Colon Cancer Cell Line. . 2023; 316 - 322. 10.33808/clinexphealthsci.1100770
Vancouver Mısırlı D,Bingöl Özakpınar Ö,şekerler t,ARU B,Yanikkaya Demirel G,Tunoglu S,Ozsavci D Effects of SPARC and Possible Receptors on Colon Cancer Cell Line. . 2023; 316 - 322. 10.33808/clinexphealthsci.1100770
IEEE Mısırlı D,Bingöl Özakpınar Ö,şekerler t,ARU B,Yanikkaya Demirel G,Tunoglu S,Ozsavci D "Effects of SPARC and Possible Receptors on Colon Cancer Cell Line." , ss.316 - 322, 2023. 10.33808/clinexphealthsci.1100770
ISNAD Mısırlı, Duygu vd. "Effects of SPARC and Possible Receptors on Colon Cancer Cell Line". (2023), 316-322. https://doi.org/10.33808/clinexphealthsci.1100770
APA Mısırlı D, Bingöl Özakpınar Ö, şekerler t, ARU B, Yanikkaya Demirel G, Tunoglu S, Ozsavci D (2023). Effects of SPARC and Possible Receptors on Colon Cancer Cell Line. Clinical and Experimental Health Sciences, 13(2), 316 - 322. 10.33808/clinexphealthsci.1100770
Chicago Mısırlı Duygu,Bingöl Özakpınar Özlem,şekerler turgut,ARU BASAK,Yanikkaya Demirel Gulderen,Tunoglu Servet,Ozsavci Derya Effects of SPARC and Possible Receptors on Colon Cancer Cell Line. Clinical and Experimental Health Sciences 13, no.2 (2023): 316 - 322. 10.33808/clinexphealthsci.1100770
MLA Mısırlı Duygu,Bingöl Özakpınar Özlem,şekerler turgut,ARU BASAK,Yanikkaya Demirel Gulderen,Tunoglu Servet,Ozsavci Derya Effects of SPARC and Possible Receptors on Colon Cancer Cell Line. Clinical and Experimental Health Sciences, vol.13, no.2, 2023, ss.316 - 322. 10.33808/clinexphealthsci.1100770
AMA Mısırlı D,Bingöl Özakpınar Ö,şekerler t,ARU B,Yanikkaya Demirel G,Tunoglu S,Ozsavci D Effects of SPARC and Possible Receptors on Colon Cancer Cell Line. Clinical and Experimental Health Sciences. 2023; 13(2): 316 - 322. 10.33808/clinexphealthsci.1100770
Vancouver Mısırlı D,Bingöl Özakpınar Ö,şekerler t,ARU B,Yanikkaya Demirel G,Tunoglu S,Ozsavci D Effects of SPARC and Possible Receptors on Colon Cancer Cell Line. Clinical and Experimental Health Sciences. 2023; 13(2): 316 - 322. 10.33808/clinexphealthsci.1100770
IEEE Mısırlı D,Bingöl Özakpınar Ö,şekerler t,ARU B,Yanikkaya Demirel G,Tunoglu S,Ozsavci D "Effects of SPARC and Possible Receptors on Colon Cancer Cell Line." Clinical and Experimental Health Sciences, 13, ss.316 - 322, 2023. 10.33808/clinexphealthsci.1100770
ISNAD Mısırlı, Duygu vd. "Effects of SPARC and Possible Receptors on Colon Cancer Cell Line". Clinical and Experimental Health Sciences 13/2 (2023), 316-322. https://doi.org/10.33808/clinexphealthsci.1100770
Sayfa Oluşturulma Tarihi
24-04-2024 14:33

İLETİŞİM

TÜBİTAK ULAKBİM TR Dizin

Yüzüncüyıl, İşçi Blokları Mahallesi

Muhsin Yazıcıoğlu Caddesi No:51/C

06530 Çankaya / ANKARA +90 (312) 298 92 00

trdizin@tubitak.gov.tr

TÜBİTAK ULAKBİM Ulusal Akademik Ağ ve Bilgi Merkezi Cahit Arf Bilgi Merkezi © Tüm Hakları Saklıdır. Gizlilik Politikası Kullanım Şartları