nach oben

Erschienen in:

07.04.2016 | Original Article

Immunohistochemical demonstration of EphA2 processing by MT1-MMP in invasive cutaneous squamous cell carcinoma

verfasst von: Ryoko Tatsukawa, Kaori Koga, Mikiko Aoki, Naohiko Koshikawa, Shinichi Imafuku, Juichiro Nakayama, Kazuki Nabeshima

Erschienen in: Virchows Archiv | Ausgabe 1/2016

Einloggen, um Zugang zu erhalten

Abstract

Erythropoietin-producing hepatocellular receptor-2 (EphA2) overexpression is prevalent in many types of human cancers, and it has been reported that high EphA2 expression is correlated with malignancy. Recent studies revealed that processing of EphA2 by cleaving off the N-terminal portion by membrane-type 1 matrix metalloproteinase (MT1-MMP) promotes invasion via stimulation of Ras in cancer cells in vitro. The objectives of this study were to investigate the presence and role of EphA2 processing in cutaneous squamous cell carcinoma (SCC) tissues. EphA2 (C-terminal and N-terminal) and MT1-MMP expression patterns and levels were analyzed immunohistochemically in SCC (n = 70) and Bowen disease (BD; n = 20). Levels of MT1-MMP and EphA2 expression were evaluated using digital image analysis. Proximity between MT1-MMP and EphA2 in cancer cells and its effect on EphA2 processing were investigated using a combination of in situ proximity ligation assay (PLA) and Western blotting. Immunohistochemical analyses showed that levels of EphA2 N-terminal expression were significantly lower than those of EphA2 C-terminal expression in SCC, whereas levels of EphA2 C- and N-terminal expression were similar in BD. Western blotting showed processed EphA2 fragments in human SCC tissues. Expression levels of MT1-MMP, EphA2, and processed EphA2 fragments were higher in SCC than BD. Proximity between MT1-MMP and EphA2 in SCC was demonstrated by in situ PLA. Our results suggest possible involvement of MT1-MMP processing of EphA2 in invasiveness of cutaneous SCC.

Teramoto Y, Nakamura Y, Yamada K, Yamamoto A (2014) Oral S-1 in advanced cutaneous squamous cell carcinoma. J Dermatol 41(6):494–497. doi:10.1111/1346-8138.12498 CrossRefPubMed

Kerkela E, Saarialho-Kere U (2003) Matrix metalloproteinases in tumor progression: focus on basal and squamous cell skin cancer. Exp Dermatol 12(2):109–125CrossRefPubMed

Roh MR, Zheng Z, Kim HS, Kwon JE, Jeung HC, Rha SY, Chung KY (2012) Differential expression patterns of MMPs and their role in the invasion of epithelial premalignant tumors and invasive cutaneous squamous cell carcinoma. Exp Mol Pathol 92(2):236–242. doi:10.1016/j.yexmp.2012.01.003 CrossRefPubMed

Hernandez-Perez M, El-hajahmad M, Massaro J, Mahalingam M (2012) Expression of gelatinases (MMP-2, MMP-9) and gelatinase activator (MMP-14) in actinic keratosis and in in situ and invasive squamous cell carcinoma. Am J Dermatopathol 34(7):723–728. doi:10.1097/DAD.0b013e31824b1ddf CrossRefPubMed

Zelinski DP, Zantek ND, Stewart JC, Irizarry AR, Kinch MS (2001) EphA2 overexpression causes tumorigenesis of mammary epithelial cells. Cancer Res 61(5):2301–2306PubMed

Thaker PH, Deavers M, Celestino J, Thornton A, Fletcher MS, Landen CN, Kinch MS, Kiener PA, Sood AK (2004) EphA2 expression is associated with aggressive features in ovarian carcinoma. Clin Cancer Res 10(15):5145–5150. doi:10.1158/1078-0432.ccr-03-0589 CrossRefPubMed

Brannan JM, Dong W, Prudkin L, Behrens C, Lotan R, Bekele BN, Wistuba I, Johnson FM (2009) Expression of the receptor tyrosine kinase EphA2 is increased in smokers and predicts poor survival in non-small cell lung cancer. Clin Cancer Res 15(13):4423–4430. doi:10.1158/1078-0432.ccr-09-0473 CrossRefPubMed

Liu F, Park PJ, Lai W, Maher E, Chakravarti A, Durso L, Jiang X, Yu Y, Brosius A, Thomas M, Chin L, Brennan C, DePinho RA, Kohane I, Carroll RS, Black PM, Johnson MD (2006) A genome-wide screen reveals functional gene clusters in the cancer genome and identifies EphA2 as a mitogen in glioblastoma. Cancer Res 66(22):10815–10823. doi:10.1158/0008-5472.can-06-1408 CrossRefPubMed

Taddei ML, Parri M, Angelucci A, Onnis B, Bianchini F, Giannoni E, Raugei G, Calorini L, Rucci N, Teti A, Bologna M, Chiarugi P (2009) Kinase-dependent and -independent roles of EphA2 in the regulation of prostate cancer invasion and metastasis. Am J Pathol 174(4):1492–1503. doi:10.2353/ajpath.2009.080473 CrossRefPubMedPubMedCentral

10.

Herrem CJ, Tatsumi T, Olson KS, Shirai K, Finke JH, Bukowski RM, Zhou M, Richmond AL, Derweesh I, Kinch MS, Storkus WJ (2005) Expression of EphA2 is prognostic of disease-free interval and overall survival in surgically treated patients with renal cell carcinoma. Clin Cancer Res 11(1):226–231PubMed

11.

Margaryan NV, Strizzi L, Abbott DE, Seftor EA, Rao MS, Hendrix MJ, Hess AR (2009) EphA2 as a promoter of melanoma tumorigenicity. Cancer Biol Ther 8(3):279–288CrossRefPubMedPubMedCentral

12.

Miyazaki T, Kato H, Fukuchi M, Nakajima M, Kuwano H (2003) EphA2 overexpression correlates with poor prognosis in esophageal squamous cell carcinoma. Int J Cancer 103(5):657–663. doi:10.1002/ijc.10860 CrossRefPubMed

13.

Shao Z, Zhang WF, Chen XM, Shang ZJ (2008) Expression of EphA2 and VEGF in squamous cell carcinoma of the tongue: correlation with the angiogenesis and clinical outcome. Oral Oncol 44(12):1110–1117. doi:10.1016/j.oraloncology.2008.01.018 CrossRefPubMed

14.

Liu Y, Zhang X, Qiu Y, Huang D, Zhang S, Xie L, Qi L, Yu C, Zhou X, Hu G, Tian Y (2011) Clinical significance of EphA2 expression in squamous-cell carcinoma of the head and neck. J Cancer Res Clin Oncol 137(5):761–769. doi:10.1007/s00432-010-0936-2 CrossRefPubMed

15.

Holm R, de Putte GV, Suo Z, Lie AK, Kristensen GB (2008) Expressions of EphA2 and EphrinA-1 in early squamous cell cervical carcinomas and their relation to prognosis. Int J Med Sci 5(3):121–126CrossRefPubMedPubMedCentral

16.

Wykosky J, Debinski W (2008) The EphA2 receptor and ephrinA1 ligand in solid tumors: function and therapeutic targeting. Mol Cancer Res 6(12):1795–1806. doi:10.1158/1541-7786.mcr-08-0244 CrossRefPubMedPubMedCentral

17.

Zhang J, Hughes S (2006) Role of the ephrin and Eph receptor tyrosine kinase families in angiogenesis and development of the cardiovascular system. J Pathol 208(4):453–461. doi:10.1002/path.1937 CrossRefPubMed

18.

Beauchamp A, Debinski W (2012) Ephs and ephrins in cancer: ephrin-A1 signalling. Semin Cell Dev Biol 23(1):109–115. doi:10.1016/j.semcdb.2011.10.019 CrossRefPubMed

19.

Wykosky J, Palma E, Gibo DM, Ringler S, Turner CP, Debinski W (2008) Soluble monomeric EphrinA1 is released from tumor cells and is a functional ligand for the EphA2 receptor. Oncogene 27(58):7260–7273. doi:10.1038/onc.2008.328 CrossRefPubMedPubMedCentral

20.

Alford S, Watson-Hurthig A, Scott N, Carette A, Lorimer H, Bazowski J, Howard PL (2010) Soluble ephrin a1 is necessary for the growth of HeLa and SK-BR3 cells. Cancer Cell Int 10:41. doi:10.1186/1475-2867-10-41 CrossRefPubMedPubMedCentral

21.

Hiramoto-Yamaki N, Takeuchi S, Ueda S, Harada K, Fujimoto S, Negishi M, Katoh H (2010) Ephexin4 and EphA2 mediate cell migration through a RhoG-dependent mechanism. J Cell Biol 190(3):461–477. doi:10.1083/jcb.201005141 CrossRefPubMedPubMedCentral

22.

Pasquale EB (2010) Eph receptors and ephrins in cancer: bidirectional signalling and beyond. Nat Rev Cancer 10(3):165–180. doi:10.1038/nrc2806 CrossRefPubMedPubMedCentral

23.

Miao H, Wang B (2012) EphA receptor signaling–complexity and emerging themes. Semin Cell Dev Biol 23(1):16–25. doi:10.1016/j.semcdb.2011.10.013 CrossRefPubMed

24.

Sugiyama N, Gucciardo E, Tatti O, Varjosalo M, Hyytiainen M, Gstaiger M, Lehti K (2013) EphA2 cleavage by MT1-MMP triggers single cancer cell invasion via homotypic cell repulsion. J Cell Biol 201(3):467–484. doi:10.1083/jcb.201205176 CrossRefPubMedPubMedCentral

25.

Koshikawa N, Hoshino D, Taniguchi H, Minegishi T, Tomari T, Nam SO, Aoki M, Sueta T, Nakagawa T, Miyamoto S, Nabeshima K, Weaver AM, Seiki M (2015) Proteolysis of EphA2 converts it from a tumor suppressor to an oncoprotein. Cancer Res 75(16):3327–3339. doi:10.1158/0008-5472.can-14-2798 CrossRefPubMed

26.

Okada A, Bellocq JP, Rouyer N, Chenard MP, Rio MC, Chambon P, Basset P (1995) Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas. Proc Natl Acad Sci U S A 92(7):2730–2734CrossRefPubMedPubMedCentral

27.

Poincloux R, Lizarraga F, Chavrier P (2009) Matrix invasion by tumour cells: a focus on MT1-MMP trafficking to invadopodia. J Cell Sci 122(Pt 17):3015–3024. doi:10.1242/jcs.034561 CrossRefPubMed

28.

Seiki M, Koshikawa N, Yana I (2003) Role of pericellular proteolysis by membrane-type 1 matrix metalloproteinase in cancer invasion and angiogenesis. Cancer Metastasis Rev 22(2–3):129–143CrossRefPubMed

29.

Seiki M (2003) Membrane-type 1 matrix metalloproteinase: a key enzyme for tumor invasion. Cancer Lett 194(1):1–11CrossRefPubMed

30.

Koshikawa N, Mizushima H, Minegishi T, Eguchi F, Yotsumoto F, Nabeshima K, Miyamoto S, Mekada E, Seiki M (2011) Proteolytic activation of heparin-binding EGF-like growth factor by membrane-type matrix metalloproteinase-1 in ovarian carcinoma cells. Cancer Sci 102(1):111–116. doi:10.1111/j.1349-7006.2010.01748.x CrossRefPubMed

31.

Xiaoyin H, Jiandon W, Qian S, Haijin F, Xiaoxiang G, Jinghua W (2013) EphA2/CD10/Bcl-6/MUM1 contributes to subclassification of diffuse large B cell lymphoma. J Transl Med 1(3):101–106

32.

Chu MB, Slutsky JB, Dhandha MM, Beal BT, Armbrecht ES, Walker RJ, Varvares MA, Fosko SW (2014) Evaluation of the definitions of "high-risk" cutaneous squamous cell carcinoma using the American Joint Committee on Cancer staging criteria and National Comprehensive Cancer Network guidelines. J Skin Cancer 2014:154340. doi:10.1155/2014/154340 CrossRefPubMedPubMedCentral

33.

Lisabeth EM, Falivelli G, Pasquale EB (2013) Eph receptor signaling and ephrins. Cold Spring Harb Perspect Biol 5(9). doi:10.1101/cshperspect.a009159

34.

Weedon D, Morgan M. B, Gross C, Nagore E, Yu L (2003) World Health Organization Classification of Tumours. Pathology and genetics of skin tumours. IARC Press, Lyon

35.

Holm R, Knopp S, Suo Z, Trope C, Nesland JM (2007) Expression of EphA2 and EphrinA-1 in vulvar carcinomas and its relation to prognosis. J Clin Pathol 60(10):1086–1091. doi:10.1136/jcp.2006.041194 CrossRefPubMed

36.

Ishikawa M, Miyahara R, Sonobe M, Horiuchi M, Mennju T, Nakayama E, Kobayashi M, Kikuchi R, Kitamura J, Imamura N, Huang CL, Date H (2012) Higher expression of EphA2 and ephrin-A1 is related to favorable clinicopathological features in pathological stage I non-small cell lung carcinoma. Lung Cancer 76(3):431–438. doi:10.1016/j.lungcan.2011.12.004 CrossRefPubMed

37.

Trudel D, Desmeules P, Turcotte S, Plante M, Gregoire J, Renaud MC, Orain M, Bairati I, Tetu B (2014) Visual and automated assessment of matrix metalloproteinase-14 tissue expression for the evaluation of ovarian cancer prognosis. Mod Pathol 27(10):1394–1404. doi:10.1038/modpathol.2014.32 CrossRefPubMed

38.

Braun M, Kirsten R, Rupp NJ, Moch H, Fend F, Wernert N, Kristiansen G, Perner S (2013) Quantification of protein expression in cells and cellular subcompartments on immunohistochemical sections using a computer supported image analysis system. Histol Histopathol 28(5):605–610PubMed

39.

Dennis J, Parsa R, Chau D, Koduru P, Peng Y, Fang Y, Sarode VR (2015) Quantification of human epidermal growth factor receptor 2 immunohistochemistry using the Ventana Image Analysis System: correlation with gene amplification by fluorescence in situ hybridization: the importance of instrument validation for achieving high (>95 %) concordance rate. Am J Surg Pathol 39(5):624–631. doi:10.1097/pas.0000000000000375 CrossRefPubMed

Titel: Immunohistochemical demonstration of EphA2 processing by MT1-MMP in invasive cutaneous squamous cell carcinoma
verfasst von: Ryoko Tatsukawa
Kaori Koga
Mikiko Aoki
Naohiko Koshikawa
Shinichi Imafuku
Juichiro Nakayama
Kazuki Nabeshima
Publikationsdatum: 07.04.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Virchows Archiv / Ausgabe 1/2016
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-016-1934-9

Neu im Fachgebiet Pathologie

01.04.2024 | Forensische Traumatologie | CME

Springer Medizin

Immunohistochemical demonstration of EphA2 processing by MT1-MMP in invasive cutaneous squamous cell carcinoma

Abstract

Neu im Fachgebiet Pathologie

Theoretische Grundlagen von Explosionen und Explosionsverletzungen

Auswirkungen vorgeschalteter Laborprozesse auf die Digitalisierung histologischer Schnittpräparate

Knochenmarkhistologie bei Zytopenien

Herausforderungen der Automation bei der quantitativen Auswertung von Leberbiopsien

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2016

Gene promoter hypermethylation is found in sentinel lymph nodes of breast cancer patients, in samples identified as positive by one-step nucleic acid amplification of cytokeratin 19 mRNA

Postmortem CT is more accurate than clinical diagnosis for identifying the immediate cause of death in hospitalized patients: a prospective autopsy-based study

HOXB13 expression in metastatic prostate cancer

Primary pulmonary clear cell sarcoma—the first two reported cases

Expression of miR-146a, miR-155, and miR-223 in formalin-fixed paraffin-embedded synovial tissues of patients with rheumatoid arthritis and osteoarthritis

“Mucin”-secreting papillary renal cell carcinoma: clinicopathological, immunohistochemical, and molecular genetic analysis of seven cases

Neu im Fachgebiet Pathologie

Theoretische Grundlagen von Explosionen und Explosionsverletzungen

Auswirkungen vorgeschalteter Laborprozesse auf die Digitalisierung histologischer Schnittpräparate

Knochenmarkhistologie bei Zytopenien

Herausforderungen der Automation bei der quantitativen Auswertung von Leberbiopsien