Skip to main content
Top
Published in: Clinical & Experimental Metastasis 6/2014

01-08-2014 | Research Paper

High expression of S100A4 and endoglin is associated with metastatic disease in head and neck squamous cell carcinoma

Authors: Marcos Vinícius Macedo de Oliveira, Carlos Alberto de Carvalho Fraga, Lucas Oliveira Barros, Camila Santos Pereira, Sérgio Henrique Sousa Santos, John R. Basile, Ricardo Santiago Gomez, André Luiz Sena Guimarães, Alfredo Maurício Batista De-Paula

Published in: Clinical & Experimental Metastasis | Issue 6/2014

Login to get access

Abstract

The presence of cervical metastasis is responsible for high morbidity and mortality rates in individuals with head and neck squamous cell carcinoma (HNSCC). S100A4, a pleiotropic EF-hand calcium-binding protein, is expressed in various normal and cancer cell types. During cancer progression, molecular disturbances in S100A4 can modulate the activity and expression of pre-metastatic and metastatic genes. In this study, we investigated the association between S100A4 methylation status and protein expression as well as the expression of the S100A4 related-proteins annexin A2 (ANXA2), matrix metallopeptidase-9, and endoglin, for metastasis and other clinicopathological parameters in HNSCC. Formalin-fixed, paraffin-embedded blocks of metastatic and non-metastatic HNSCC and matched cervical lymph node (LN) samples (metastatic LN = mLN, non-metastatic = nmLN, and control LN (lymphadenitis) = cLN) were submitted for methylation specific-polymerase chain reaction and immunohistochemistry. Our results showed that S100A4 methylation status failed to demonstrate association with cervical metastasis and other clinicopathological factors related to HNSCC. HNSCC samples from patients that presented with metastatic disease showed high S100A4 and endoglin expression (p < 0.05). In conclusion, molecular disturbances in S100A4 and endoglin expression might regulate the formation of cervical metastasis in HNSCC.
Appendix
Available only for authorised users
Literature
4.
go back to reference De Paula AM, Souza LR, Farias LC, Correa GT, Fraga CA, Eleuterio NB, Silveira AC, Santos FB, Haikal DS, Guimaraes AL, Gomez RS (2009) Analysis of 724 cases of primary head and neck squamous cell carcinoma (HNSCC) with a focus on young patients and p53 immunolocalization. Oral Oncol 45(9):777–782PubMedCrossRef De Paula AM, Souza LR, Farias LC, Correa GT, Fraga CA, Eleuterio NB, Silveira AC, Santos FB, Haikal DS, Guimaraes AL, Gomez RS (2009) Analysis of 724 cases of primary head and neck squamous cell carcinoma (HNSCC) with a focus on young patients and p53 immunolocalization. Oral Oncol 45(9):777–782PubMedCrossRef
6.
11.
go back to reference Donato R (2001) S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles. Int J Biochem Cell Biol 33(7):637–668PubMed Donato R (2001) S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles. Int J Biochem Cell Biol 33(7):637–668PubMed
12.
go back to reference Polans AS, Palczewski K, Asson-Batres MA, Ohguro H, Witkowska D, Haley TL, Baizer L, Crabb JW (1994) Purification and primary structure of Capl, an S-100-related calcium-binding protein isolated from bovine retina. J Biol Chem 269(8):6233–6240PubMed Polans AS, Palczewski K, Asson-Batres MA, Ohguro H, Witkowska D, Haley TL, Baizer L, Crabb JW (1994) Purification and primary structure of Capl, an S-100-related calcium-binding protein isolated from bovine retina. J Biol Chem 269(8):6233–6240PubMed
14.
go back to reference Garrett SC, Varney KM, Weber DJ, Bresnick AR (2006) S100A4, a mediator of metastasis. J Biol Chem 281(2):677–680PubMedCrossRef Garrett SC, Varney KM, Weber DJ, Bresnick AR (2006) S100A4, a mediator of metastasis. J Biol Chem 281(2):677–680PubMedCrossRef
19.
20.
go back to reference Rodriguez-Manzaneque JC, Lane TF, Ortega MA, Hynes RO, Lawler J, Iruela-Arispe ML (2001) Thrombospondin-1 suppresses spontaneous tumor growth and inhibits activation of matrix metalloproteinase-9 and mobilization of vascular endothelial growth factor. Proc Natl Acad Sci U S A 98(22):12485–12490. doi:10.1073/pnas.171460498 PubMedCentralPubMedCrossRef Rodriguez-Manzaneque JC, Lane TF, Ortega MA, Hynes RO, Lawler J, Iruela-Arispe ML (2001) Thrombospondin-1 suppresses spontaneous tumor growth and inhibits activation of matrix metalloproteinase-9 and mobilization of vascular endothelial growth factor. Proc Natl Acad Sci U S A 98(22):12485–12490. doi:10.​1073/​pnas.​171460498 PubMedCentralPubMedCrossRef
21.
go back to reference Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, Tamaki K, Tanzawa K, Thorpe P, Itohara S, Werb Z, Hanahan D (2000) Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2(10):737–744. doi:10.1038/35036374 PubMedCentralPubMed Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, Tamaki K, Tanzawa K, Thorpe P, Itohara S, Werb Z, Hanahan D (2000) Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2(10):737–744. doi:10.​1038/​35036374 PubMedCentralPubMed
22.
go back to reference Ramos-DeSimone N, Hahn-Dantona E, Sipley J, Nagase H, French DL, Quigley JP (1999) Activation of matrix metalloproteinase-9 (MMP-9) via a converging plasmin/stromelysin-1 cascade enhances tumor cell invasion. J Biol Chem 274(19):13066–13076PubMedCrossRef Ramos-DeSimone N, Hahn-Dantona E, Sipley J, Nagase H, French DL, Quigley JP (1999) Activation of matrix metalloproteinase-9 (MMP-9) via a converging plasmin/stromelysin-1 cascade enhances tumor cell invasion. J Biol Chem 274(19):13066–13076PubMedCrossRef
23.
go back to reference Yu Q, Stamenkovic I (2000) Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev 14(2):163–176PubMedCentralPubMed Yu Q, Stamenkovic I (2000) Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev 14(2):163–176PubMedCentralPubMed
24.
go back to reference Fonsatti E, Maio M (2004) Highlights on endoglin (CD105): from basic findings towards clinical applications in human cancer. J Trans Med 2(1):18CrossRef Fonsatti E, Maio M (2004) Highlights on endoglin (CD105): from basic findings towards clinical applications in human cancer. J Trans Med 2(1):18CrossRef
25.
go back to reference Li DY, Sorensen LK, Brooke BS, Urness LD, Davis EC, Taylor DG, Boak BB, Wendel DP (1999) Defective angiogenesis in mice lacking endoglin. Science 284(5419):1534–1537PubMedCrossRef Li DY, Sorensen LK, Brooke BS, Urness LD, Davis EC, Taylor DG, Boak BB, Wendel DP (1999) Defective angiogenesis in mice lacking endoglin. Science 284(5419):1534–1537PubMedCrossRef
27.
go back to reference She X, Matsuno F, Harada N, Tsai H, Seon BK (2004) Synergy between anti-endoglin (CD105) monoclonal antibodies and TGF-beta in suppression of growth of human endothelial cells. Int J Cancer 108(2):251–257. doi:10.1002/ijc.11551 PubMed She X, Matsuno F, Harada N, Tsai H, Seon BK (2004) Synergy between anti-endoglin (CD105) monoclonal antibodies and TGF-beta in suppression of growth of human endothelial cells. Int J Cancer 108(2):251–257. doi:10.​1002/​ijc.​11551 PubMed
29.
go back to reference Saad RS, Liu YL, Nathan G, Celebrezze J, Medich D, Silverman JF (2004) Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer. Mod Pathol 17(2):197–203PubMedCrossRef Saad RS, Liu YL, Nathan G, Celebrezze J, Medich D, Silverman JF (2004) Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer. Mod Pathol 17(2):197–203PubMedCrossRef
30.
31.
go back to reference Moriyama-Kita M, Endo Y, Yonemura Y, Heizmann CW, Schafer BW, Sasaki T, Yamamoto E (2004) Correlation of S100A4 expression with invasion and metastasis in oral squamous cell carcinoma. Oral Oncol 40(5):496–500PubMedCrossRef Moriyama-Kita M, Endo Y, Yonemura Y, Heizmann CW, Schafer BW, Sasaki T, Yamamoto E (2004) Correlation of S100A4 expression with invasion and metastasis in oral squamous cell carcinoma. Oral Oncol 40(5):496–500PubMedCrossRef
32.
go back to reference Sapkota D, Bruland O, Boe OE, Bakeer H, Elgindi OA, Vasstrand EN, Ibrahim SO (2008) Expression profile of the S100 gene family members in oral squamous cell carcinomas. JOral PatholMed 37(10):607–615. doi:10.1111/j.1600-0714.2008.00683.x Sapkota D, Bruland O, Boe OE, Bakeer H, Elgindi OA, Vasstrand EN, Ibrahim SO (2008) Expression profile of the S100 gene family members in oral squamous cell carcinomas. JOral PatholMed 37(10):607–615. doi:10.​1111/​j.​1600-0714.​2008.​00683.​x
34.
go back to reference Bryne M, Koppang HS, Lilleng R, Kjaerheim A (1992) Malignancy grading of the deep invasive margins of oral squamous cell carcinomas has high prognostic value. J Pathol 166(4):375–381PubMedCrossRef Bryne M, Koppang HS, Lilleng R, Kjaerheim A (1992) Malignancy grading of the deep invasive margins of oral squamous cell carcinomas has high prognostic value. J Pathol 166(4):375–381PubMedCrossRef
37.
go back to reference Vermeulen PB, Gasparini G, Fox SB, Toi M, Martin L, McCulloch P, Pezzella F, Viale G, Weidner N, Harris AL, Dirix LY (1996) Quantification of angiogenesis in solid human tumours: an international consensus on the methodology and criteria of evaluation. Eur J Cancer 32A(14):2474–2484PubMedCrossRef Vermeulen PB, Gasparini G, Fox SB, Toi M, Martin L, McCulloch P, Pezzella F, Viale G, Weidner N, Harris AL, Dirix LY (1996) Quantification of angiogenesis in solid human tumours: an international consensus on the methodology and criteria of evaluation. Eur J Cancer 32A(14):2474–2484PubMedCrossRef
38.
40.
go back to reference Baylin SB, Esteller M, Rountree MR, Bachman KE, Schuebel K, Herman JG (2001) Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum Mol Genet 10(7):687–692PubMedCrossRef Baylin SB, Esteller M, Rountree MR, Bachman KE, Schuebel K, Herman JG (2001) Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum Mol Genet 10(7):687–692PubMedCrossRef
42.
go back to reference Li Y, Liu ZL, Zhang KL, Chen XY, Kong QY, Wu ML, Sun Y, Liu J, Li H (2009) Methylation-associated silencing of S100A4 expression in human epidermal cancers. Exp Dermatol 18(10):842–848PubMedCrossRef Li Y, Liu ZL, Zhang KL, Chen XY, Kong QY, Wu ML, Sun Y, Liu J, Li H (2009) Methylation-associated silencing of S100A4 expression in human epidermal cancers. Exp Dermatol 18(10):842–848PubMedCrossRef
43.
go back to reference Liu J, Guo Y, Fu S, Yang M, Sun KL, Fu WN (2010) Hypomethylation-induced expression of S100A4 increases the invasiveness of laryngeal squamous cell carcinoma. Oncol Rep 23(4):1101–1107PubMedCrossRef Liu J, Guo Y, Fu S, Yang M, Sun KL, Fu WN (2010) Hypomethylation-induced expression of S100A4 increases the invasiveness of laryngeal squamous cell carcinoma. Oncol Rep 23(4):1101–1107PubMedCrossRef
44.
go back to reference Xie R, Loose DS, Shipley GL, Xie S, Bassett RL Jr, Broaddus RR (2007) Hypomethylation-induced expression of S100A4 in endometrial carcinoma. Mod Pathol 20(10):1045–1054PubMedCrossRef Xie R, Loose DS, Shipley GL, Xie S, Bassett RL Jr, Broaddus RR (2007) Hypomethylation-induced expression of S100A4 in endometrial carcinoma. Mod Pathol 20(10):1045–1054PubMedCrossRef
45.
go back to reference Matos LL, Trufelli DC, de Matos MG, da Silva Pinhal MA (2010) Immunohistochemistry as an important tool in biomarkers detection and clinical practice. Biomark Insights 5:9–20PubMedCentralPubMedCrossRef Matos LL, Trufelli DC, de Matos MG, da Silva Pinhal MA (2010) Immunohistochemistry as an important tool in biomarkers detection and clinical practice. Biomark Insights 5:9–20PubMedCentralPubMedCrossRef
46.
go back to reference Moriyama-Kita M, Endo Y, Yonemura Y, Heizmann CW, Miyamori H, Sato H, Yamamoto E, Sasaki T (2005) S100A4 regulates E-cadherin expression in oral squamous cell carcinoma. Cancer Lett 230(2):211–218PubMedCrossRef Moriyama-Kita M, Endo Y, Yonemura Y, Heizmann CW, Miyamori H, Sato H, Yamamoto E, Sasaki T (2005) S100A4 regulates E-cadherin expression in oral squamous cell carcinoma. Cancer Lett 230(2):211–218PubMedCrossRef
48.
go back to reference Li ZH, Bresnick AR (2006) The S100A4 metastasis factor regulates cellular motility via a direct interaction with myosin-IIA. Cancer Res 66(10):5173–5180PubMedCrossRef Li ZH, Bresnick AR (2006) The S100A4 metastasis factor regulates cellular motility via a direct interaction with myosin-IIA. Cancer Res 66(10):5173–5180PubMedCrossRef
49.
go back to reference Bjornland K, Winberg JO, Odegaard OT, Hovig E, Loennechen T, Aasen AO, Fodstad O, Maelandsmo GM (1999) S100A4 involvement in metastasis: deregulation of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in osteosarcoma cells transfected with an anti-S100A4 ribozyme. Cancer Res 59(18):4702–4708PubMed Bjornland K, Winberg JO, Odegaard OT, Hovig E, Loennechen T, Aasen AO, Fodstad O, Maelandsmo GM (1999) S100A4 involvement in metastasis: deregulation of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in osteosarcoma cells transfected with an anti-S100A4 ribozyme. Cancer Res 59(18):4702–4708PubMed
50.
go back to reference Schmidt-Hansen B, Ornas D, Grigorian M, Klingelhofer J, Tulchinsky E, Lukanidin E, Ambartsumian N (2004) Extracellular S100A4(mts1) stimulates invasive growth of mouse endothelial cells and modulates MMP-13 matrix metalloproteinase activity. Oncogene 23(32):5487–5495PubMedCrossRef Schmidt-Hansen B, Ornas D, Grigorian M, Klingelhofer J, Tulchinsky E, Lukanidin E, Ambartsumian N (2004) Extracellular S100A4(mts1) stimulates invasive growth of mouse endothelial cells and modulates MMP-13 matrix metalloproteinase activity. Oncogene 23(32):5487–5495PubMedCrossRef
51.
go back to reference Semov A, Moreno MJ, Onichtchenko A, Abulrob A, Ball M, Ekiel I, Pietrzynski G, Stanimirovic D, Alakhov V (2005) Metastasis-associated protein S100A4 induces angiogenesis through interaction with annexin II and accelerated plasmin formation. JBiolChem 280(21):20833–20841 Semov A, Moreno MJ, Onichtchenko A, Abulrob A, Ball M, Ekiel I, Pietrzynski G, Stanimirovic D, Alakhov V (2005) Metastasis-associated protein S100A4 induces angiogenesis through interaction with annexin II and accelerated plasmin formation. JBiolChem 280(21):20833–20841
52.
go back to reference Oh SP, Seki T, Goss KA, Imamura T, Yi Y, Donahoe PK, Li L, Miyazono K, ten Dijke P, Kim S, Li E (2000) Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis. Proc Natl Acad Sci U S A 97(6):2626–2631PubMedCentralPubMedCrossRef Oh SP, Seki T, Goss KA, Imamura T, Yi Y, Donahoe PK, Li L, Miyazono K, ten Dijke P, Kim S, Li E (2000) Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis. Proc Natl Acad Sci U S A 97(6):2626–2631PubMedCentralPubMedCrossRef
53.
go back to reference Fraga CA, De Oliveira MV, de Oliveira ES, Barros LO, Santos FB, Gomez RS, De-Paula AM, Guimaraes AL (2011) A high HIF-1alpha expression genotype is associated with poor prognosis of upper aerodigestive tract carcinoma patients. Oral Oncol. doi:10.1016/j.oraloncology.2011.08.023 PubMed Fraga CA, De Oliveira MV, de Oliveira ES, Barros LO, Santos FB, Gomez RS, De-Paula AM, Guimaraes AL (2011) A high HIF-1alpha expression genotype is associated with poor prognosis of upper aerodigestive tract carcinoma patients. Oral Oncol. doi:10.​1016/​j.​oraloncology.​2011.​08.​023 PubMed
55.
58.
go back to reference Rucci N, Sanita P, Angelucci A (2011) Roles of metalloproteases in metastatic niche. Curr Mol Med 11(8):609–622PubMedCrossRef Rucci N, Sanita P, Angelucci A (2011) Roles of metalloproteases in metastatic niche. Curr Mol Med 11(8):609–622PubMedCrossRef
Metadata
Title
High expression of S100A4 and endoglin is associated with metastatic disease in head and neck squamous cell carcinoma
Authors
Marcos Vinícius Macedo de Oliveira
Carlos Alberto de Carvalho Fraga
Lucas Oliveira Barros
Camila Santos Pereira
Sérgio Henrique Sousa Santos
John R. Basile
Ricardo Santiago Gomez
André Luiz Sena Guimarães
Alfredo Maurício Batista De-Paula
Publication date
01-08-2014
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 6/2014
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-014-9655-4

Other articles of this Issue 6/2014

Clinical & Experimental Metastasis 6/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine