FasR and FasL in colorectal cancer

Szarynska,Magdalena; Olejniczak,Agata; Wierzbicki,Piotr; Kobiela,Jaroslaw; Laski,Dariusz; Sledzinski,Zbigniew; Adrych,Krystian; Guzek,Marek; Kmiec,Zbigniew

doi:10.3892/ijo.2017.4083

FasR and FasL in colorectal cancer

Authors:
- Magdalena Szarynska
- Agata Olejniczak
- Piotr Wierzbicki
- Jaroslaw Kobiela
- Dariusz Laski
- Zbigniew Sledzinski
- Krystian Adrych
- Marek Guzek
- Zbigniew Kmiec
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Affiliations: Department of Histology, Medical University of Gdansk, 80-210 Gdansk, Poland, Department of General, Endocrine and Transplant Surgery, Medical University of Gdansk, Invasive Medicine Centre, 80-214 Gdansk, Poland, Department of Hepatology and Gastroenterology, Medical University of Gdansk, Invasive Medicine Centre, 80-214 Gdansk, Poland
Published online on: July 27, 2017 https://doi.org/10.3892/ijo.2017.4083
Pages: 975-986

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Abstract

Colorectal cancer (CRC) is one of the most common solid organ cancers prevalent worldwide causing, in spite of advancing therapeutic methodology, high rate of patient mortality, especially due to metastasis development. The cancer stem cell (CSC) theory of tumor growth indicates that CSCs within the tumor mass have great capacity to initiate and sustain tumor growth. Following the suggestion that Fas signaling can be engaged in apoptosis, tumor maintenance, senescence or DICE (death induced by CD95 or CD95L elimination), the attempts to broaden the knowledge concerning the relationships between CSCs features and FasR/FasL appeared to be necessary. The most important advantage of our study was the simultaneously analysis of CSCs from commonly used CRC lines (HCT116 and HT29) and tumor fragments collected from CRC patients. Moreover, the sphere-promoting expansion of CRC lines brought a specific three-dimensional specific environment for CSC exploration. We further investigated the function of Fas signaling in CRC lines depending on the culture mode as we incubated HCT116 and HT29 cells with anti-FasR agonistic antibodies. It appeared to act in a line-dependent and culture mode-dependent manner and influenced some particular features of CSCs such as spherogenicity, proliferation and phenotype. Additionally, the analysis of mRNA level showed that disease progression is associated with significantly increased expression of FasR and/or FasL. In conclusion, our observation seems to confirm that spherical model of cancer lines is more reliable for some sophisticated analysis because of their greater resemblance to the CSCs from human CRC samples in comparison to commonly used adherent cells, at least according to aspects of their biology analyzed in this study. That can be extended to the resemblance of in vitro sphere forming conditions to the in vivo environment. However, the greatest difference concerns the level of apoptosis, thus, this issue require further experiments.

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1	Reya T, Morrison SJ, Clarke MF and Weissman IL: Stem cells, cancer, and cancer stem cells. Nature. 414:105–111. 2001. View Article : Google Scholar : PubMed/NCBI
2	Charafe-Jauffret E, Ginestier C and Birnbaum D: Breast cancer stem cells: Tools and models to rely on. BMC Cancer. 9:2022009. View Article : Google Scholar : PubMed/NCBI
3	Creighton CJ, Li X, Landis M, Dixon JM, Neumeister VM, Sjolund A, Rimm DL, Wong H, Rodriguez A, Herschkowitz JI, et al: Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci USA. 106:13820–13825. 2009. View Article : Google Scholar : PubMed/NCBI
4	Gupta PB, Chaffer CL and Weinberg RA: Cancer stem cells: Mirage or reality? Nat Med. 15:1010–1012. 2009. View Article : Google Scholar : PubMed/NCBI
5	Frank NY, Schatton T and Frank MH: The therapeutic promise of the cancer stem cell concept. J Clin Invest. 120:41–50. 2010. View Article : Google Scholar : PubMed/NCBI
6	Peter ME, Hadji A, Murmann AE, Brockway S, Putzbach W, Pattanayak A and Ceppi P: The role of CD95 and CD95 ligand in cancer. Cell Death Differ. 22:885–886. 2015. View Article : Google Scholar : PubMed/NCBI
7	Ogasawara J, Watanabe-Fukunaga R, Adachi M, Matsuzawa A, Kasugai T, Kitamura Y, Itoh N, Suda T and Nagata S: Lethal effect of the anti-Fas antibody in mice. Nature. 364:806–809. 1993. View Article : Google Scholar : PubMed/NCBI
8	Martin-Villalba A, Llorens-Bobadilla E and Wollny D: CD95 in cancer: Tool or target? Trends Mol Med. 19:329–335. 2013. View Article : Google Scholar : PubMed/NCBI
9	Chen L, Park SM, Tumanov AV, Hau A, Sawada K, Feig C, Turner JR, Fu YX, Romero IL, Lengyel E, et al: CD95 promotes tumour growth. Nature. 465:492–496. 2010. View Article : Google Scholar : PubMed/NCBI
10	Desbarats J and Newell MK: Fas engagement accelerates liver regeneration after partial hepatectomy. Nat Med. 6:920–923. 2000. View Article : Google Scholar : PubMed/NCBI
11	Jarad G, Wang B, Khan S, DeVore J, Miao H, Wu K, Nishimura SL, Wible BA, Konieczkowski M, Sedor JR, et al: Fas activation induces renal tubular epithelial cell beta 8 integrin expression and function in the absence of apoptosis. J Biol Chem. 277:47826–47833. 2002. View Article : Google Scholar : PubMed/NCBI
12	Desbarats J, Birge RB, Mimouni-Rongy M, Weinstein DE, Palerme JS and Newell MK: Fas engagement induces neurite growth through ERK activation and p35 upregulation. Nat Cell Biol. 5:118–125. 2003. View Article : Google Scholar : PubMed/NCBI
13	Zuliani C, Kleber S, Klussmann S, Wenger T, Kenzelmann M, Schreglmann N, Martinez A, del Rio JA, Soriano E, Vodrazka P, et al: Control of neuronal branching by the death receptor CD95 (Fas/Apo-1). Cell Death Differ. 13:31–40. 2006. View Article : Google Scholar
14	Corsini NS, Sancho-Martinez I, Laudenklos S, Glagow D, Kumar S, Letellier E, Koch P, Teodorczyk M, Kleber S, Klussmann S, et al: The death receptor CD95 activates adult neural stem cells for working memory formation and brain repair. Cell Stem Cell. 5:178–190. 2009. View Article : Google Scholar : PubMed/NCBI
15	Siegmund D, Lang I and Wajant H: Cell death-independent activities of the death receptors CD95, TRAILR1, and TRAILR2. FEBS J. 284:1131–1159. 2017. View Article : Google Scholar
16	Ceppi P, Hadji A, Kohlhapp FJ, Pattanayak A, Hau A, Liu X, Liu H, Murmann AE and Peter ME: CD95 and CD95L promote and protect cancer stem cells. Nat Commun. 5:52382014. View Article : Google Scholar : PubMed/NCBI
17	Teodorczyk M, Kleber S, Wollny D, Sefrin JP, Aykut B, Mateos A, Herhaus P, Sancho-Martinez I, Hill O, Gieffers C, et al: CD95 promotes metastatic spread via Sck in pancreatic ductal adenocarcinoma. Cell Death Differ. 22:1192–1202. 2015. View Article : Google Scholar : PubMed/NCBI
18	Drachsler M, Kleber S, Mateos A, Volk K, Mohr N, Chen S, Cirovic B, Tüttenberg J, Gieffers C, Sykora J, et al: CD95 maintains stem cell-like and non-classical EMT programs in primary human glioblastoma cells. Cell Death Dis. 7:e22092016. View Article : Google Scholar : PubMed/NCBI
19	Li H, Fan X, Stoicov C, Liu JH, Zubair S, Tsai E, Ste Marie R, Wang TC, Lyle S, Kurt-Jones E, et al: Human and mouse colon cancer utilizes CD95 signaling for local growth and metastatic spread to liver. Gastroenterology. 137:934–944. 944.e931–934. 2009. View Article : Google Scholar : PubMed/NCBI
20	Hoogwater FJ, Nijkamp MW, Smakman N, Steller EJ, Emmink BL, Westendorp BF, Raats DA, Sprick MR, Schaefer U, Van Houdt WJ, et al: Oncogenic K-Ras turns death receptors into metastasis-promoting receptors in human and mouse colorectal cancer cells. Gastroenterology. 138:2357–2367. 2010. View Article : Google Scholar : PubMed/NCBI
21	Kykalos S, Mathaiou S, Karayiannakis AJ, Patsouras D, Lambropoulou M and Simopoulos C: Tissue expression of the proteins fas and fas ligand in colorectal cancer and liver metastases. J Gastrointest Cancer. 43:224–228. 2012. View Article : Google Scholar
22	Nijkamp MW, Hoogwater FJ, Steller EJ, Westendorp BF, van der Meulen TA, Leenders MW, Borel Rinkes IH and Kranenburg O: CD95 is a key mediator of invasion and accelerated outgrowth of mouse colorectal liver metastases following radiofrequency ablation. J Hepatol. 53:1069–1077. 2010. View Article : Google Scholar : PubMed/NCBI
23	Sträter J, Hinz U, Hasel C, Bhanot U, Mechtersheimer G, Lehnert T and Möller P: Impaired CD95 expression predisposes for recurrence in curatively resected colon carcinoma: Clinical evidence for immunoselection and CD95L mediated control of minimal residual disease. Gut. 54:661–665. 2005. View Article : Google Scholar : PubMed/NCBI
24	Zhang W, Ding EX, Wang Q, Zhu DQ, He J, Li YL and Wang YH: Fas ligand expression in colon cancer: A possible mechanism of tumor immune privilege. World J Gastroenterol. 11:3632–3635. 2005. View Article : Google Scholar : PubMed/NCBI
25	Hadji A, Ceppi P, Murmann AE, Brockway S, Pattanayak A, Bhinder B, Hau A, De Chant S, Parimi V, Kolesza P, et al: Death induced by CD95 or CD95 ligand elimination. Cell Rep. 7:208–222. 2014. View Article : Google Scholar : PubMed/NCBI
26	Weiswald LB, Bellet D and Dangles-Marie V: Spherical cancer models in tumor biology. Neoplasia. 17:1–15. 2015. View Article : Google Scholar : PubMed/NCBI
27	Hirschhaeuser F, Menne H, Dittfeld C, West J, Mueller-Klieser W and Kunz-Schughart LA: Multicellular tumor spheroids: An underestimated tool is catching up again. J Biotechnol. 148:3–15. 2010. View Article : Google Scholar : PubMed/NCBI
28	Chandrasekaran S, Marshall JR, Messing JA, Hsu JW and King MR: TRAIL-mediated apoptosis in breast cancer cells cultured as 3D spheroids. PLoS One. 9:e1114872014. View Article : Google Scholar : PubMed/NCBI
29	Endo H, Okami J, Okuyama H, Kumagai T, Uchida J, Kondo J, Takehara T, Nishizawa Y, Imamura F, Higashiyama M, et al: Spheroid culture of primary lung cancer cells with neuregulin 1/HER3 pathway activation. J Thorac Oncol. 8:131–139. 2013. View Article : Google Scholar : PubMed/NCBI
30	Tong JG, Valdes YR, Barrett JW, Bell JC, Stojdl D, McFadden G, McCart JA, DiMattia GE and Shepherd TG: Evidence for differential viral oncolytic efficacy in an in vitro model of epithelial ovarian cancer metastasis. Mol Ther Oncolytics. 2:150132015. View Article : Google Scholar : PubMed/NCBI
31	Qureshi-Baig K, Ullmann P, Rodriguez F, Frasquilho S, Nazarov PV, Haan S and Letellier E: What do we learn from spheroid culture systems? Insights from tumorspheres derived from primary colon cancer tissue. PLoS One. 11:e01460522016. View Article : Google Scholar : PubMed/NCBI
32	Raats DA, Frenkel N, van Schelven SJ, Rinkes IH, Laoukili J and Kranenburg O: CD95 ligand induces senescence in mismatch repair-deficient human colon cancer via chronic caspase-mediated induction of DNA damage. Cell Death Dis. 8:e26692017. View Article : Google Scholar : PubMed/NCBI
33	Wierzbicki PM, Adrych K, Kartanowicz D, Stanislawowski M, Kowalczyk A, Godlewski J, Skwierz-Bogdanska I, Celinski K, Gach T, Kulig J, et al: Underexpression of LATS1 TSG in colorectal cancer is associated with promoter hypermethylation. World J Gastroenterol. 19:4363–4373. 2013. View Article : Google Scholar : PubMed/NCBI
34	Schmittgen TD and Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 3:1101–1108. 2008. View Article : Google Scholar : PubMed/NCBI
35	O'Reilly LA1, Tai L, Lee L, Kruse EA, Grabow S, Fairlie WD, Haynes NM, Tarlinton DM, Zhang JG, Belz GT, et al: Membrane-bound Fas ligand only is essential for Fas-induced apoptosis. Nature. 461:659–663. 2009. View Article : Google Scholar
36	Todaro M, Francipane MG, Medema JP and Stassi G: Colon cancer stem cells: Promise of targeted therapy. Gastroenterology. 138:2151–2162. 2010. View Article : Google Scholar : PubMed/NCBI
37	Schickel R, Park SM, Murmann AE and Peter ME: miR-200c regulates induction of apoptosis through CD95 by targeting FAP-1. Mol Cell. 38:908–915. 2010. View Article : Google Scholar : PubMed/NCBI
38	Steller EJ, Ritsma L, Raats DA, Hoogwater FJ, Emmink BL, Govaert KM, Laoukili J, Rinkes IH, van Rheenen J and Kranenburg O: The death receptor CD95 activates the cofilin pathway to stimulate tumour cell invasion. EMBO Rep. 12:931–937. 2011. View Article : Google Scholar : PubMed/NCBI
39	Hong S, Kim S, Kim HY, Kang M, Jang HH and Lee WS: Targeting the PI3K signaling pathway in KRAS mutant colon cancer. Cancer Med. 5:248–255. 2016. View Article : Google Scholar :
40	Élez E, Kocáková I, Höhler T, Martens UM, Bokemeyer C, Van Cutsem E, Melichar B, Smakal M, Csőszi T, Topuzov E, et al: Abituzumab combined with cetuximab plus irinotecan versus cetuximab plus irinotecan alone for patients with KRAS wild-type metastatic colorectal cancer: The randomised phase I/II POSEIDON trial. Ann Oncol. 26:132–140. 2015. View Article : Google Scholar
41	Igney FH and Krammer PH: Tumor counterattack: Fact or fiction? Cancer Immunol Immunother. 54:1127–1136. 2005. View Article : Google Scholar : PubMed/NCBI
42	O'Connell J, O'Sullivan GC, Collins JK and Shanahan F: The Fas counterattack: Fas-mediated T cell killing by colon cancer cells expressing Fas ligand. J Exp Med. 184:1075–1082. 1996. View Article : Google Scholar : PubMed/NCBI
43	Igney FH and Krammer PH: Death and anti-death: Tumour resistance to apoptosis. Nat Rev Cancer. 2:277–288. 2002. View Article : Google Scholar : PubMed/NCBI
44	Hoogwater FJ, Snoeren N, Nijkamp MW, Gunning AC, van Houdt WJ, DE Bruijn MT, Voest EE, van Hillegersberg R, Kranenburg O and Rinkes IH: Circulating CD95-ligand as a potential prognostic marker for recurrence in patients with synchronous colorectal liver metastases. Anticancer Res. 31:4507–4512. 2011.PubMed/NCBI
45	Konno R, Takano T, Sato S and Yajima A: Serum soluble fas level as a prognostic factor in patients with gynecological malignancies. Clin Cancer Res. 6:3576–3580. 2000.PubMed/NCBI