Skip to main content
Erschienen in: Pathology & Oncology Research 2/2017

14.09.2016 | Original Article

Expression of ADAM10, Fas, FasL and Soluble FasL in Patients with Oral Squamous Cell Carcinoma (OSCC) and their Association with Clinical-Pathological Parameters

verfasst von: José Sergio Zepeda-Nuño, Celia Guerrero-Velázquez, Susana Del Toro-Arreola, Natali Vega-Magaña, Julián Ángeles-Sánchez, Jesse Haramati, Ana L. Pereira-Suárez, Miriam R. Bueno-Topete

Erschienen in: Pathology & Oncology Research | Ausgabe 2/2017

Einloggen, um Zugang zu erhalten

Abstract

ADAM10 has been implicated in the progression of various solid tumors. ADAM10 regulates the cleavage of the FasL ectodomain from the plasma membrane of different cell types, generating the soluble FasL fragment (sFasL). Currently, there are few studies in oral squamous cell carcinoma (OSCC) that correlate levels of ADAM10 and FasL in the tumor microenvironment with clinical parameters of the disease. To determine the expression of ADAM10, Fas, FasL and sFasL in patients with OSCC and its association with TNM stage. Twenty-five patients with OSCC and 25 healthy controls were included. Biopsies of tumor tissue from patients with OSCC and buccal mucosa in controls were obtained. ADAM10, Fas, and FasL were analyzed by Western blotting. sFasL was quantified by ELISA. ADAM10 and Fas decreased significantly in OSCC compared with controls. Relatedly, within the OSCC group, Fas and ADAM10 decreased in accordance with tumor disease stage; in stages I/II, as well as in tumors of smaller diameter (T1-T2), ADAM10 showed higher levels when compared to patients with T3-T4 tumors and in stage III-IV. FasL in the tumor microenvironment and serum FasL showed no significant differences between both groups. Levels of complete FasL and cleaved FasL were positively correlated in controls; this correlation is preserved in patients with tumors in early stages (I-II), but is lost in later stage (III-IV). The dysregulation of ADAM10, Fas and FasL could be useful indicators of the progression and severity of OSCC.
Literatur
1.
2.
Zurück zum Zitat Fong D, Spizzo G, Gostner JM, Gastl G, Moser P, Krammel C, Gerhard S, Rasse M, Laimer K (2008) TROP2: a novel prognostic marker in squamous cell carcinoma of the oral cavity. Mod Pathol 21:186–191PubMed Fong D, Spizzo G, Gostner JM, Gastl G, Moser P, Krammel C, Gerhard S, Rasse M, Laimer K (2008) TROP2: a novel prognostic marker in squamous cell carcinoma of the oral cavity. Mod Pathol 21:186–191PubMed
3.
Zurück zum Zitat Edwards DR, Handsley MM, Pennington CJ (2008) The ADAM metalloproteinases. Mol Asp Med 29:258–289CrossRef Edwards DR, Handsley MM, Pennington CJ (2008) The ADAM metalloproteinases. Mol Asp Med 29:258–289CrossRef
4.
Zurück zum Zitat Tousseyn T, Thathiah A, Jorissen E, Raemaekers T, Konietzko U, Reiss K, Maes E, Snellinx A, Serneels L, Nyabi O, Annaert W, Saftig P, Hartmann D, De Strooper B (2009) ADAM10, the rate-limiting protease of regulated intramembrane proteolysis of notch and other proteins, is processed by ADAMS-9, ADAMS-15, and the gamma-secretase. J Biol Chem 284:11738–11747CrossRefPubMedPubMedCentral Tousseyn T, Thathiah A, Jorissen E, Raemaekers T, Konietzko U, Reiss K, Maes E, Snellinx A, Serneels L, Nyabi O, Annaert W, Saftig P, Hartmann D, De Strooper B (2009) ADAM10, the rate-limiting protease of regulated intramembrane proteolysis of notch and other proteins, is processed by ADAMS-9, ADAMS-15, and the gamma-secretase. J Biol Chem 284:11738–11747CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Mochizuki S, Okada Y (2007) ADAMs in cancer cell proliferation and progression. Cancer Sci 98:621–628CrossRefPubMed Mochizuki S, Okada Y (2007) ADAMs in cancer cell proliferation and progression. Cancer Sci 98:621–628CrossRefPubMed
6.
Zurück zum Zitat Jones A, Lambert D, Speight P, Whawell S (2013) ADAM 10 is over expressed in oral squamous cell carcinoma and contributes to invasive behavior through a functional association with avb6 integrin. FEBS Lett 587:3529–3534CrossRefPubMed Jones A, Lambert D, Speight P, Whawell S (2013) ADAM 10 is over expressed in oral squamous cell carcinoma and contributes to invasive behavior through a functional association with avb6 integrin. FEBS Lett 587:3529–3534CrossRefPubMed
7.
Zurück zum Zitat Ko SY, Lin SC, Wong YK, Liu CJ, Chang KW, Liu TY (2007) Increase of disintergin metalloprotease 10 (ADAM10) expression in oral squamous cell carcinoma. Cancer Lett 245:33–43CrossRefPubMed Ko SY, Lin SC, Wong YK, Liu CJ, Chang KW, Liu TY (2007) Increase of disintergin metalloprotease 10 (ADAM10) expression in oral squamous cell carcinoma. Cancer Lett 245:33–43CrossRefPubMed
8.
Zurück zum Zitat Pruessmeyer J, Ludwig A (2009) The good, the bad and the ugly substrates for ADAM10 and ADAM17 in brain pathology, inflammation and cancer. Semin Cell Dev Biol 20:164–174CrossRefPubMed Pruessmeyer J, Ludwig A (2009) The good, the bad and the ugly substrates for ADAM10 and ADAM17 in brain pathology, inflammation and cancer. Semin Cell Dev Biol 20:164–174CrossRefPubMed
10.
Zurück zum Zitat Schulte M, Reiss K, Lettau M, Maretzky T, Ludwig A, Hartmann D, de Strooper B, Janssen O, Saftig P (2007) ADAM10 regulates FasL cell surface expression and modulates FasL-induced cytotoxicity and activation-induced cell death. Cell Death Differ 14:1040–1049PubMed Schulte M, Reiss K, Lettau M, Maretzky T, Ludwig A, Hartmann D, de Strooper B, Janssen O, Saftig P (2007) ADAM10 regulates FasL cell surface expression and modulates FasL-induced cytotoxicity and activation-induced cell death. Cell Death Differ 14:1040–1049PubMed
11.
Zurück zum Zitat Kirkin V, Cahuzac N, Guardiola-Serrano F, Huault S, Lückerath K, Friedmann E, Novac N, Wels WS, Martoglio B, Hueber AO, Zörnig M (2007) The Fas ligand intracellular domain is released by ADAM10 and SPPL2a cleavage in T-cells. Cell Death Differ 14:1678–1687CrossRefPubMed Kirkin V, Cahuzac N, Guardiola-Serrano F, Huault S, Lückerath K, Friedmann E, Novac N, Wels WS, Martoglio B, Hueber AO, Zörnig M (2007) The Fas ligand intracellular domain is released by ADAM10 and SPPL2a cleavage in T-cells. Cell Death Differ 14:1678–1687CrossRefPubMed
12.
Zurück zum Zitat Peter ME, Hadji A, Murmann AE, Brockway S, Putzbach W, Pattanayak A, Ceppi P (2015) The role of CD95 and CD95 ligand in cancer. Cell Death Differ 22:549–559CrossRefPubMedPubMedCentral Peter ME, Hadji A, Murmann AE, Brockway S, Putzbach W, Pattanayak A, Ceppi P (2015) The role of CD95 and CD95 ligand in cancer. Cell Death Differ 22:549–559CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Pietras K, Ostman A (2010) Hallmarks of cancer: interactions with the tumor stromal. Exp Cell Res 316:1324–1331CrossRefPubMed Pietras K, Ostman A (2010) Hallmarks of cancer: interactions with the tumor stromal. Exp Cell Res 316:1324–1331CrossRefPubMed
14.
Zurück zum Zitat Gaida MM, Haag N, Günther F, Tschaharganeh DF, Schirmacher P, Friess H, Giese NA, Schmidt J, Wente MN (2010) Expression of a disintegrin and metalloprotease 10 in pancreatic carcinoma. Int J Mol Med 26:281–288PubMed Gaida MM, Haag N, Günther F, Tschaharganeh DF, Schirmacher P, Friess H, Giese NA, Schmidt J, Wente MN (2010) Expression of a disintegrin and metalloprotease 10 in pancreatic carcinoma. Int J Mol Med 26:281–288PubMed
15.
Zurück zum Zitat You B, Shan Y, Shi S, Li X, You Y (2015) Effects of ADAM10 upregulation on progression, migration, and prognosis of nasopharyngeal carcinoma. Cancer Sci 106:1506–1514CrossRefPubMedPubMedCentral You B, Shan Y, Shi S, Li X, You Y (2015) Effects of ADAM10 upregulation on progression, migration, and prognosis of nasopharyngeal carcinoma. Cancer Sci 106:1506–1514CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Guo J, He L, Yuan P, Wang P, Lu Y, Tong F, Wang Y, Yin Y, Tian J, Sun J (2012) ADAM10 overexpression in human non-small cell lung cancer correlates with cell migration and invasion through the activation of the Notch1 signaling pathway. Oncol Rep 28:1709–1718PubMed Guo J, He L, Yuan P, Wang P, Lu Y, Tong F, Wang Y, Yin Y, Tian J, Sun J (2012) ADAM10 overexpression in human non-small cell lung cancer correlates with cell migration and invasion through the activation of the Notch1 signaling pathway. Oncol Rep 28:1709–1718PubMed
17.
Zurück zum Zitat Shaker M, Yokoyama Y, Mori S, Tsujimoto M, Kawaguchi N, Kiyono T, Nakano T, Matsuura N (2011) Aberrant expression of disintegrin-metalloprotease proteins in the formation and progression of uterine cervical cancer. Pathobiology 78:149–161CrossRefPubMed Shaker M, Yokoyama Y, Mori S, Tsujimoto M, Kawaguchi N, Kiyono T, Nakano T, Matsuura N (2011) Aberrant expression of disintegrin-metalloprotease proteins in the formation and progression of uterine cervical cancer. Pathobiology 78:149–161CrossRefPubMed
18.
Zurück zum Zitat Saftig P, Reiss K (2011) The "a disintegrin and metalloproteases" ADAM10 and ADAM17: novel drug targets with therapeutic potential? Eur J Cell Biol 90:527–535 Saftig P, Reiss K (2011) The "a disintegrin and metalloproteases" ADAM10 and ADAM17: novel drug targets with therapeutic potential? Eur J Cell Biol 90:527–535
19.
Zurück zum Zitat Weber S, Niessen MT, Prox J, Lüllmann-Rauch R, Schmitz A, Schwanbeck R, Blobel CP, Jorissen E, de Strooper B, Niessen CM, Saftig P (2011) The disintegrin/metalloproteinase Adam10 is essential for epidermal integrity and Notch-mediated signaling. Development 138:495–505CrossRefPubMedPubMedCentral Weber S, Niessen MT, Prox J, Lüllmann-Rauch R, Schmitz A, Schwanbeck R, Blobel CP, Jorissen E, de Strooper B, Niessen CM, Saftig P (2011) The disintegrin/metalloproteinase Adam10 is essential for epidermal integrity and Notch-mediated signaling. Development 138:495–505CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Ebsen H, Schröder A, Kabelitz D, Janssen O (2013) Differential surface expression of ADAM10 and ADAM17 on human T lymphocytes and tumor cells. PLoS One 8:e76853CrossRefPubMedPubMedCentral Ebsen H, Schröder A, Kabelitz D, Janssen O (2013) Differential surface expression of ADAM10 and ADAM17 on human T lymphocytes and tumor cells. PLoS One 8:e76853CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Pabois A, Devallière J, Quillard T, Coulon F, Gérard N, Laboisse C, Toquet C, Charreau B (2014) The disintegrin and metalloproteinase ADAM10 mediates a canonical notch-dependent regulation of IL-6 through Dll4 in human endothelial cells. Biochem Pharmacol 91:510–521CrossRefPubMed Pabois A, Devallière J, Quillard T, Coulon F, Gérard N, Laboisse C, Toquet C, Charreau B (2014) The disintegrin and metalloproteinase ADAM10 mediates a canonical notch-dependent regulation of IL-6 through Dll4 in human endothelial cells. Biochem Pharmacol 91:510–521CrossRefPubMed
22.
Zurück zum Zitat Zhuang J, Wei Q, Lin Z, Zhou C (2015) Effects of ADAM10 deletion on notch-1 signaling pathway and neuronal maintenance in adult mouse brain. Gene 555:150–158CrossRefPubMed Zhuang J, Wei Q, Lin Z, Zhou C (2015) Effects of ADAM10 deletion on notch-1 signaling pathway and neuronal maintenance in adult mouse brain. Gene 555:150–158CrossRefPubMed
23.
Zurück zum Zitat Scholz F, Schulte A, Adamski F, Hundhausen C, Mittag J, Schwarz A, Kruse ML, Proksch E, Ludwig A (2007) Constitutive expression and regulated release of the transmembrane chemokine CXCL16 in human and murine skin. J Invest Dermatol 127:1444–1455CrossRefPubMed Scholz F, Schulte A, Adamski F, Hundhausen C, Mittag J, Schwarz A, Kruse ML, Proksch E, Ludwig A (2007) Constitutive expression and regulated release of the transmembrane chemokine CXCL16 in human and murine skin. J Invest Dermatol 127:1444–1455CrossRefPubMed
24.
Zurück zum Zitat Abel S, Hundhausen C, Mentlein R, Schulte A, Berkhout TA, Broadway N, Hartmann D, Sedlacek R, Dietrich S, Muetze B, Schuster B, Kallen KJ, Saftig P, Rose-John S, Ludwig A (2004) The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10. J Immunol 172:6362–6372CrossRefPubMed Abel S, Hundhausen C, Mentlein R, Schulte A, Berkhout TA, Broadway N, Hartmann D, Sedlacek R, Dietrich S, Muetze B, Schuster B, Kallen KJ, Saftig P, Rose-John S, Ludwig A (2004) The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10. J Immunol 172:6362–6372CrossRefPubMed
25.
Zurück zum Zitat Gregory MS, Hackett CG, Abernathy EF, Lee KS, Saff RR, Hohlbaum AM, Moody KS, Hobson MW, Jones A, Kolovou P, Karray S, Giani A, John SW, Chen DF, Marshak-Rothstein A, Ksander BR (2011) Opposing roles for membrane bound and soluble Fas ligand in glaucoma-associated retinal ganglion cell death. PLoS One 6:e17659 Gregory MS, Hackett CG, Abernathy EF, Lee KS, Saff RR, Hohlbaum AM, Moody KS, Hobson MW, Jones A, Kolovou P, Karray S, Giani A, John SW, Chen DF, Marshak-Rothstein A, Ksander BR (2011) Opposing roles for membrane bound and soluble Fas ligand in glaucoma-associated retinal ganglion cell death. PLoS One 6:e17659
26.
Zurück zum Zitat Wisniewski P, Ellert-Miklaszewska A, Kwiatkowska A, Kaminska B (2010) Non-apoptotic Fas signaling regulates invasiveness of glioma cells and modulates MMP-2 activity via NFkappaB-TIMP-2 pathway. Cell Signal 22:212–220CrossRefPubMed Wisniewski P, Ellert-Miklaszewska A, Kwiatkowska A, Kaminska B (2010) Non-apoptotic Fas signaling regulates invasiveness of glioma cells and modulates MMP-2 activity via NFkappaB-TIMP-2 pathway. Cell Signal 22:212–220CrossRefPubMed
27.
Zurück zum Zitat Hoffmann TK, Dworacki G, Tsukihiro T, Meidenbauer N, Gooding W, Johnson JT, Whiteside TL (2002) Spontaneous apoptosis of circulating T lymphocytes in patients with head and neck cancer and its clinical importance. Clin Cancer Res 8:2553–2562PubMed Hoffmann TK, Dworacki G, Tsukihiro T, Meidenbauer N, Gooding W, Johnson JT, Whiteside TL (2002) Spontaneous apoptosis of circulating T lymphocytes in patients with head and neck cancer and its clinical importance. Clin Cancer Res 8:2553–2562PubMed
28.
Zurück zum Zitat Jabłońska E, Kiersnowska-Rogowska B, Rogowski F, Parfieńczyk A, Puzewska W, Bukin M (2005) Soluble form of TRAIL, Fas and FasL in the serum of patients with B-CLL. Rocz Akad Med Bialymst 50:204–207PubMed Jabłońska E, Kiersnowska-Rogowska B, Rogowski F, Parfieńczyk A, Puzewska W, Bukin M (2005) Soluble form of TRAIL, Fas and FasL in the serum of patients with B-CLL. Rocz Akad Med Bialymst 50:204–207PubMed
29.
Zurück zum Zitat Askenasy N, Yolcu ES, Yaniv I, Shirwan H (2005) Induction of tolerance using Fas ligand: a double-edged immunomodulator. Blood 105:1396–1404CrossRefPubMed Askenasy N, Yolcu ES, Yaniv I, Shirwan H (2005) Induction of tolerance using Fas ligand: a double-edged immunomodulator. Blood 105:1396–1404CrossRefPubMed
30.
Zurück zum Zitat Mogi M, Fukuo K, Yang J, Suhara T, Ogihara T (2001) Hypoxia stimulates release of the soluble form of fas ligand that inhibits endothelial cell apoptosis. Lab Investig 81:177–184CrossRefPubMed Mogi M, Fukuo K, Yang J, Suhara T, Ogihara T (2001) Hypoxia stimulates release of the soluble form of fas ligand that inhibits endothelial cell apoptosis. Lab Investig 81:177–184CrossRefPubMed
31.
Zurück zum Zitat Fang L, Sun L, FF H, Chen QE (2013) Effects of FasL expression in oral squamous cell cancer. Asian Pac J Cancer Prev 14:281–285CrossRefPubMed Fang L, Sun L, FF H, Chen QE (2013) Effects of FasL expression in oral squamous cell cancer. Asian Pac J Cancer Prev 14:281–285CrossRefPubMed
32.
Zurück zum Zitat Das SN, Khare P, Singh MK, Sharma SC (2011) Fas receptor (CD95) & Fas ligand (CD178) expression in patients with tobacco-related intraoral squamous cell carcinoma. Indian J Med Res 134:54–60PubMedPubMedCentral Das SN, Khare P, Singh MK, Sharma SC (2011) Fas receptor (CD95) & Fas ligand (CD178) expression in patients with tobacco-related intraoral squamous cell carcinoma. Indian J Med Res 134:54–60PubMedPubMedCentral
33.
Zurück zum Zitat Lee SH, Jang JJ, Lee JY, Kim SY, Park WS, Shin MS, Dong SM, Na EY, Kim KM, Kim CS, Kim SH, Yoo NJ (1998) Fas ligand is expressed in normal skin and in some cutaneous malignancies. Br J Dermatol 139:186–191CrossRefPubMed Lee SH, Jang JJ, Lee JY, Kim SY, Park WS, Shin MS, Dong SM, Na EY, Kim KM, Kim CS, Kim SH, Yoo NJ (1998) Fas ligand is expressed in normal skin and in some cutaneous malignancies. Br J Dermatol 139:186–191CrossRefPubMed
Metadaten
Titel
Expression of ADAM10, Fas, FasL and Soluble FasL in Patients with Oral Squamous Cell Carcinoma (OSCC) and their Association with Clinical-Pathological Parameters
verfasst von
José Sergio Zepeda-Nuño
Celia Guerrero-Velázquez
Susana Del Toro-Arreola
Natali Vega-Magaña
Julián Ángeles-Sánchez
Jesse Haramati
Ana L. Pereira-Suárez
Miriam R. Bueno-Topete
Publikationsdatum
14.09.2016
Verlag
Springer Netherlands
Erschienen in
Pathology & Oncology Research / Ausgabe 2/2017
Print ISSN: 1219-4956
Elektronische ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-016-0102-5

Weitere Artikel der Ausgabe 2/2017

Pathology & Oncology Research 2/2017 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.