Ectodomain shedding of the cell adhesion molecule Nectin-4 in ovarian cancer is mediated by ADAM10 and ADAM17

Journal of Biological Chemistry

Volumn 292, Issue 15, 2017, Pages 6339-6351

  Buchanan, Petra C ^a   Boylan, Kristin L M ^a   Walcheck, Bruce ^a,b   Heinze, Rachel ^a   Geller, Melissa A ^b   Argenta, Peter A ^b   Skubitz, Amy P N ^a  

^a UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF MINNESOTA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOMARKERS; BIOMOLECULES; BODY FLUIDS; CELL ADHESION; CELLS; CYTOLOGY; ENZYME ACTIVITY; GENE EXPRESSION; MOLECULES; PHOSPHOLIPIDS; TUMORS;

CELL ADHESION MOLECULES; EXTRACELLULAR DOMAINS; LYSOPHOSPHATIDIC ACID; OVARIAN CANCER CELLS; PROGRESSION FREE SURVIVAL; SMALL MOLECULE INHIBITOR; THERAPEUTIC TARGETS; TRANS-MEMBRANE PROTEINS;

DISEASES;

ADAM10 ENDOPEPTIDASE; CELL ADHESION MOLECULE; EPIDERMAL GROWTH FACTOR RECEPTOR; LYSOPHOSPHATIDIC ACID; MITOGEN ACTIVATED PROTEIN KINASE 12; MITOGEN ACTIVATED PROTEIN KINASE 3; MITOGEN ACTIVATED PROTEIN KINASE P38; NECTIN 4; PROTEIN C JUN; PROTEIN KINASE B; RNA; SMALL INTERFERING RNA; STRESS ACTIVATED PROTEIN KINASE 1; TUMOR NECROSIS FACTOR ALPHA CONVERTING ENZYME; UNCLASSIFIED DRUG; ADAM10 PROTEIN, HUMAN; ADAM17 PROTEIN, HUMAN; LNIR PROTEIN, HUMAN; MEMBRANE PROTEIN; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE; SECRETASE;

ARTICLE; ASCITES CELL; ASCITES FLUID LEVEL; CELL SURFACE; CONTROLLED STUDY; ECTODOMAIN SHEDDING; ENZYME PHOSPHORYLATION; EPITHELIUM CELL; FEMALE; HUMAN; HUMAN CELL; NIH OVCAR5 CELL LINE; OMENTUM; OVARIAN CANCER CELL LINE; OVARY CANCER; PERITONEUM METASTASIS; PROGRESSION FREE SURVIVAL; PROTEIN BLOOD LEVEL; PROTEIN CLEAVAGE; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; SIGNAL TRANSDUCTION; GENETICS; METABOLISM; METASTASIS; OVARY TUMOR; PATHOLOGY; TUMOR CELL LINE;

ADAM10 PROTEIN; ADAM17 PROTEIN; AMYLOID PRECURSOR PROTEIN SECRETASES; CELL ADHESION MOLECULES; CELL LINE, TUMOR; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; FEMALE; HUMANS; MAP KINASE SIGNALING SYSTEM; MEMBRANE PROTEINS; NEOPLASM METASTASIS; OVARIAN NEOPLASMS; PROTEIN DOMAINS; PROTO-ONCOGENE PROTEINS C-AKT; PROTO-ONCOGENE PROTEINS C-JUN; RNA, MESSENGER; RNA, NEOPLASM;

EID: 85018510352     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M116.746859     Document Type: Article

References (68)

1. Siegel, R. L., Miller, K. D., and Jemal, A. (2015) Cancer statistics, 2015. CA Cancer J. Clin. 65, 5-29.
2. Perets, R., and Drapkin, R. (2016) It's totally tubular: Riding the new wave of ovarian cancer research. Cancer Res. 76, 10-17.
3. Pradeep, S., Kim, S. W., Wu, S. Y., Nishimura, M., Chaluvally-Raghavan, P., Miyake, T., Pecot, C. V., Kim, S. J., Choi, H. J., Bischoff, F. Z., Mayer, J. A., Huang, L., Nick, A. M., Hall, C. S., Rodriguez-Aguayo, C., et al. (2014) Hematogenous metastasis of ovarian cancer: Rethinking mode of spread. Cancer Cell 26, 77-91.
4. Burleson, K. M., Casey, R. C., Skubitz, K. M., Pambuccian, S. E., Oegema, T. R. Jr., and Skubitz, A. P. (2004) Ovarian carcinoma ascites spheroids adhere to extracellular matrix components and mesothelial cell monolayers. Gynecol. Oncol. 93, 170-181.
5. Burleson, K. M., Hansen, L. K., and Skubitz, A. P. (2004) Ovarian carcinoma spheroids disaggregate on type I collagen and invade live human mesothelial cell monolayers. Clin. Exp. Metastasis 21, 685-697.
6. Burleson, K. M., Boente, M. P., Pambuccian, S. E., and Skubitz, A. P. (2006) Disaggregation and invasion of ovarian carcinoma ascites spheroids. J. Transl. Med. 4, 6.
7. Challita-Eid, P. M., Satpayev, D., Yang, P., An, Z., Morrison, K., Shostak, Y., Raitano, A., Nadell, R., Liu, W., Lortie, D. R., Capo, L., Verlinsky, A., Leavitt, M., Malik, F., Aviña, H., et al. (2016) Enfortumab vedotin antibody- drug conjugate targeting Nectin-4 is a highly potent therapeutic agent in multiple preclinical cancer models. Cancer Res. 76, 3003-3013.
8. Hibbs, K., Skubitz, K. M., Pambuccian, S. E., Casey, R. C., Burleson, K. M., Oegema, T. R. Jr., Thiele, J. J., Grindle, S. M., Bliss, R. L., and Skubitz, A. P. (2004) Differential gene expression in ovarian carcinoma: identification of potential biomarkers. Am. J. Pathol. 165, 397-414.
9. Derycke, M. S., Pambuccian, S. E., Gilks, C. B., Kalloger, S. E., Ghidouche, A., Lopez, M., Bliss, R. L., Geller, M. A., Argenta, P. A., Harrington, K. M., and Skubitz, A. P. (2010) Nectin 4 overexpression in ovarian cancer tissues and serum: potential role as a serum biomarker. Am. J. Clin. Pathol. 134, 835-845.
10. Nabih, E. S., Abdel Motaleb, F. I., and Salama, F. A. (2014) The diagnostic efficacy of nectin 4 expression in ovarian cancer patients. Biomarkers 19, 498-504.
11. Nishiwada, S., Sho, M., Yasuda, S., Shimada, K., Yamato, I., Akahori, T., Kinoshita, S., Nagai, M., Konishi, N., and Nakajima, Y. (2015) Nectin-4 expression contributes to tumor proliferation, angiogenesis and patient prognosis in human pancreatic cancer. J. Exp. Clin. Cancer Res. 34, 30.
12. Lattanzio, R., Ghasemi, R., Brancati, F., Sorda, R. L., Tinari, N., Perracchio, L., Iacobelli, S., Mottolese, M., Natali, P. G., and Piantelli, M. (2014) Membranous Nectin-4 expression is a risk factor for distant relapse of T1-T2, N0 luminal-A early breast cancer. Oncogenesis 3, e118.
13. Takano, A., Ishikawa, N., Nishino, R., Masuda, K., Yasui, W., Inai, K., Nishimura, H., Ito, H., Nakayama, H., Miyagi, Y., Tsuchiya, E., Kohno, N., Nakamura, Y., and Daigo, Y. (2009) Identification of nectin-4 oncoprotein as a diagnostic and therapeutic target for lung cancer. Cancer Res. 69, 6694-6703.
14. Kurita, S., Ogita, H., and Takai, Y. (2011) Cooperative role of nectin-nectin and nectin-Afadin interactions in formation of nectin-based cell-cell adhesion. J. Biol. Chem. 286, 36297-36303.
15. Boylan, K. L., Buchanan, P. C., Manion, R. D., Shukla, D. M., Braumberger, K., Bruggemeyer, C., and Skubitz, A. P. (2017) The expression of Nectin-4 on the surface of ovarian cancer cells alters their ability to adhere, migrate, aggregate, and proliferate. Oncotarget 8, 9717-9738.
16. Pavlova, N. N., Pallasch, C., Elia, A. E., Braun, C. J., Westbrook, T. F., Hemann, M., and Elledge, S. J. (2013) A role for PVRL4-driven cell-cell interactions in tumorigenesis. Elife 2, e00358.
17. Ogita, H., and Takai, Y. (2008) Cross-Talk among integrin, cadherin, and growth factor receptor: Roles of nectin and nectin-like molecule. Int. Rev. Cytol. 265, 1-54.
18. Fabre-Lafay, S., Garrido-Urbani, S., Reymond, N., Gonçalves, A., Dubreuil, P., and Lopez, M. (2005) Nectin-4, a new serological breast cancer marker, is a substrate for tumor necrosis factor-converting enzyme (TACE)/ADAM-17. J. Biol. Chem. 280, 19543-19550.
19. Fabre-Lafay, S., Monville, F., Garrido-Urbani, S., Berruyer-Pouyet, C., Ginestier, C., Reymond, N., Finetti, P., Sauvan, R., Adélaïde, J., Geneix, J., Lecocq, E., Popovici, C., Dubreuil, P., Viens, P., Gonçalves, A., et al. (2007) Nectin-4 is a new histological and serological tumor associated marker for breast cancer. BMC Cancer 7, 73.
20. Mullooly, M., McGowan, P. M., Crown, J., and Duffy, M. J. (2016) The ADAMs family of proteases as targets for the treatment of cancer. Cancer Biol. Ther. 17, 870-880.
21. Seals, D. F., and Courtneidge, S. A. (2003) The ADAMs family of metalloproteases: multidomain proteins with multiple functions. Genes Dev. 17, 7-30.
22. Horiuchi, K., Le Gall, S., Schulte, M., Yamaguchi, T., Reiss, K., Murphy, G., Toyama, Y., Hartmann, D., Saftig, P., and Blobel, C. P. (2007) Substrate selectivity of epidermal growth factor-receptor ligand sheddases and their regulation by phorbol esters and calcium influx. Mol. Biol. Cell 18, 176 -188.
23. 2 influx and PKC activation. J. Cell Biol. 165, 893-902.
24. Zheng, Y., Saftig, P., Hartmann, D., and Blobel, C. (2004) Evaluation of the contribution of different ADAMs to tumor necrosis factor (TNF) shedding and of the function of the TNF-ectodomain in ensuring selective stimulated shedding by the TNF-convertase (TACE/ADAM17). J. Biol. Chem. 279, 42898-42906.
25. Jing, Y., Ni, Z., Wu, J., Higgins, L., Markowski, T. W., Kaufman, D. S., and Walcheck, B. (2015) Identification of an ADAM17 cleavage region in human CD16 (Fc-RIII) and the engineering of a non-cleavable version of the receptor in NK cells. PLoS One 10, e0121788.
26. Mullooly, M., McGowan, P. M., Kennedy, S. A., Madden, S. F., Crown, J., O'Donovan, N., and Duffy, M. J. (2015) ADAM10: A new player in breast cancer progression? Br. J. Cancer 113, 945-951.
27. Yuan, S., Lei, S., and Wu, S. (2013) ADAM10 is overexpressed in human hepatocellular carcinoma and contributes to the proliferation, invasion and migration of HepG2 cells. Oncol. Rep. 30, 1715-1722.
28. McGowan, P. M., McKiernan, E., Bolster, F., Ryan, B. M., Hill, A. D., McDermott, E. W., Evoy, D., O'Higgins, N., Crown, J., and Duffy, M. J. (2008) ADAM-17 predicts adverse outcome in patients with breast cancer. Ann. Oncol. 19, 1075-1081.
29. Gyorffy, B., Lánczky, A., and Szállási, Z. (2012) Implementing an online tool for genome-wide validation of survival-Associated biomarkers in ovarian-cancer using microarray data from 1287 patients. Endocr. Relat. Cancer 19, 197-208.
30. Le Gall, S. M., Bobé, P., Reiss, K., Horiuchi, K., Niu, X. D., Lundell, D., Gibb, D. R., Conrad, D., Saftig, P., and Blobel, C. P. (2009) ADAMs 10 and 17 represent differentially regulated components of a general shedding machinery for membrane proteins such as transforming growth factor, L-selectin, and tumor necrosis factor . Mol. Biol. Cell 20, 1785-1794.
31. Sheppard, G. S., Florjancic, A. S., Giesler, J. R., Xu, L., Guo, Y., Davidsen, S. K., Marcotte, P. A., Elmore, I., Albert, D. H., Magoc, T. J., Bouska, J. J., Goodfellow, C. L., Morgan, D. W., and Summers, J. B. (1998) Aryl ketones as novel replacements for the C-Terminal amide bond of succinyl hydroxamate MMP inhibitors. Bioorg. Med. Chem. Lett. 8, 3251-3256.
32. Georgiadis, D., and Yiotakis, A. (2008) Specific targeting of metzincin family members with small-molecule inhibitors: progress toward a multifarious challenge. Bioorg. Med. Chem. 16, 8781-8794.
33. Ott, G. R., Asakawa, N., Lu, Z., Anand, R., Liu, R. Q., Covington, M. B., Vaddi, K., Qian, M., Newton, R. C., Christ, D. D., Trzaskos, J. M., and Duan, J. J. (2008) Potent, exceptionally selective, orally bioavailable inhibitors of TNF-converting enzyme (TACE): novel 2-substituted-1Hbenzo[ d]imidazol-1-yl)methyl)benzamide P1-substituents. Bioorg. Med. Chem. Lett. 18, 1577-1582.
34. Wang, Y., Wu, J., Newton, R., Bahaie, N. S., Long, C., and Walcheck, B. (2013) ADAM17 cleaves CD16b (Fc-RIIIb) in human neutrophils. Biochim. Biophys. Acta 1833, 680-685.
35. Tape, C. J., Willems, S. H., Dombernowsky, S. L., Stanley, P. L., Fogarasi, M., Ouwehand, W., McCafferty, J., and Murphy, G. (2011) Crossdomain inhibition of TACE ectodomain. Proc. Natl. Acad. Sci. U.S.A. 108, 5578 -5583.
36. Hundhausen, C., Misztela, D., Berkhout, T. A., Broadway, N., Saftig, P., Reiss, K., Hartmann, D., Fahrenholz, F., Postina, R., Matthews, V., Kallen, K. J., Rose-John, S., and Ludwig, A. (2003) The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion. Blood 102, 1186-1195.
37. Cerami, E., Gao, J., Dogrusoz, U., Gross, B. E., Sumer, S. O., Aksoy, B. A., Jacobsen, A., Byrne, C. J., Heuer, M. L., Larsson, E., Antipin, Y., Reva, B., Goldberg, A. P., Sander, C., and Schultz, N. (2012) The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2, 401-404.
38. Gao, J., Aksoy, B. A., Dogrusoz, U., Dresdner, G., Gross, B., Sumer, S. O., Sun, Y., Jacobsen, A., Sinha, R., Larsson, E., Cerami, E., Sander, C., and Schultz, N. (2013) Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci. Signal. 6, p1.
39. Cancer Genome Atlas Research Network (2011) Integrated genomic analyses of ovarian carcinoma. Nature 474, 609-615.
40. Wang, Y., Herrera, A. H., Li, Y., Belani, K. K., and Walcheck, B. (2009) Regulation of mature ADAM17 by redox agents for L-selectin shedding. J. Immunol. 182, 2449-2457.
41. Wang, Y., Robertson, J. D., and Walcheck, B. (2011) Different signaling pathways stimulate a disintegrin and metalloprotease-17 (ADAM17) in neutrophils during apoptosis and activation. J. Biol. Chem. 286, 38980 -38988.
42. Lemjabbar-Alaoui, H., Sidhu, S. S., Mengistab, A., Gallup, M., and Basbaum, C. (2011) TACE/ADAM-17 phosphorylation by PKC-epsilon mediates premalignant changes in tobacco smoke-exposed lung cells. PLoS One 6, e17489.
43. Yin, J., and Yu, F. S. (2009) ERK1/2 mediate wounding-And G-proteincoupled receptor ligands-induced EGFR activation via regulatingADAM17 and HB-EGF shedding. Invest. Ophthalmol. Vis. Sci. 50, 132-139.
44. Hurst, L. A., Bunning, R. A., Sharrack, B., and Woodroofe, M. N. (2012) siRNA knockdown of ADAM-10, but not ADAM-17, significantly reduces fractalkine shedding following pro-inflammatory cytokine treatment in a human adult brain endothelial cell line. Neurosci. Lett. 521, 52-56.
45. Ren, J., Xiao, Y. J., Singh, L. S., Zhao, X., Zhao, Z., Feng, L., Rose, T. M., Prestwich, G. D., and Xu, Y. (2006) Lysophosphatidic acid is constitutively produced by human peritoneal mesothelial cells and enhances adhesion, migration, and invasion of ovarian cancer cells. Cancer Res. 66, 3006 -3014.
46. Cao, L., Zhang, Y., Fu, Z., Dong, L., Yang, S., Meng, W., Li, Y., Zhang, W., Zhang, J., Zheng, C., Zhu, H., and Fan, L. (2015) Diagnostic value of plasma lysophosphatidic acid levels in ovarian cancer patients: A case-control study and updated meta-Analysis. J. Obstet. Gynaecol. Res. 41, 1951-1958.
47. Rosendahl, M. S., Ko, S. C., Long, D. L., Brewer, M. T., Rosenzweig, B., Hedl, E., Anderson, L., Pyle, S. M., Moreland, J., Meyers, M. A., Kohno, T., Lyons, D., and Lichenstein, H. S. (1997) Identification and characterization of a pro-Tumor necrosis factor-processing enzyme from the ADAM family of zinc metalloproteases. J. Biol. Chem. 272, 24588-24593.
48. Maskos, K., Fernandez-Catalan, C., Huber, R., Bourenkov, G. P., Bartunik, H., Ellestad, G. A., Reddy, P., Wolfson, M. F., Rauch, C. T., Castner, B. J., Davis, R., Clarke, H. R., Petersen, M., Fitzner, J. N., Cerretti, D. P., et al. (1998) Crystal structure of the catalytic domain of human tumor necrosis factor-converting enzyme. Proc. Natl. Acad. Sci. U.S.A. 95, 3408-3412.
49. Le Gall, S. M., Maretzky, T., Issuree, P. D., Niu, X. D., Reiss, K., Saftig, P., Khokha, R., Lundell, D., and Blobel, C. P. (2010) ADAM17 is regulated by a rapid and reversible mechanism that controls access to its catalytic site. J. Cell Sci. 123, 3913-3922.
50. Blobel, C. P. (1997) Metalloprotease-disintegrins: links to cell adhesion and cleavage of TNF-And Notch. Cell 90, 589-592.
51. Janes, P. W., Saha, N., Barton, W. A., Kolev, M. V., Wimmer-Kleikamp, S. H., Nievergall, E., Blobel, C. P., Himanen, J. P., Lackmann, M., and Nikolov, D. B. (2005) Adam meets Eph: An ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell 123, 291-304.
52. Blobel, C. P. (2000) Remarkable roles of proteolysis on and beyond the cell surface. Curr. Opin. Cell Biol. 12, 606-612.
53. Blobel, C. P. (2005) ADAMs: key components in EGFR signalling and development. Nat. Rev. Mol. Cell Biol. 6, 32-43.
54. Lorenzen, I., Lokau, J., Korpys, Y., Oldefest, M., Flynn, C. M., Künzel, U., Garbers, C., Freeman, M., Grötzinger, J., and Düsterhöft, S. (2016) Control of ADAM17 activity by regulation of its cellular localisation. Sci. Rep. 6, 35067.
55. Poersch, A., Grassi, M. L., Carvalho, V. P., Lanfredi, G. P., Palma Cde, S., Greene, L. J., de Sousa, C. B., Carrara, H. H., Candido Dos Reis, F. J., and Faça, V. M. (2016) A proteomic signature of ovarian cancer tumor fluid identified by high-Throughput and verified by targeted proteomics. J. Proteomics 145, 226-236.
56. Ohta, H., Sato, K., Murata, N., Damirin, A., Malchinkhuu, E., Kon, J., Kimura, T., Tobo, M., Yamazaki, Y., Watanabe, T., Yagi, M., Sato, M., Suzuki, R., Murooka, H., Sakai, T., et al. (2003) Ki16425, a subtype-selective antagonist for EDG-family lysophosphatidic acid receptors. Mol. Pharmacol. 64, 994-1005.
57. McPherson, A., Roth, A., Laks, E., Masud, T., Bashashati, A., Zhang, A. W., Ha, G., Biele, J., Yap, D., Wan, A., Prentice, L. M., Khattra, J., Smith, M. A., Nielsen, C. B., Mullaly, S. C., et al. (2016) Divergent modes of clonal spread and intraperitoneal mixing in high-grade serous ovarian cancer. Nat. Genet. 48, 758-767.
58. Baudhuin, L. M., Cristina, K. L., Lu, J., and Xu, Y. (2002) Akt activation induced by lysophosphatidic acid and sphingosine-1-phosphate requires both mitogen-Activated protein kinase kinase and p38 mitogen-Activated protein kinase and is cell-line specific. Mol. Pharmacol. 62, 660-671.
59. Matte, I., Lane, D., Laplante, C., Garde-Granger, P., Rancourt, C., and Piché, A. (2015) Ovarian cancer ascites enhance the migration of patientderived peritoneal mesothelial cells via cMet pathway through HGF-dependent and -independent mechanisms. Int. J. Cancer 137, 289-298.
60. Bellacosa, A., de Feo, D., Godwin, A. K., Bell, D. W., Cheng, J. Q., Altomare, D. A., Wan, M., Dubeau, L., Scambia, G., Masciullo, V., Ferrandina, G., Benedetti Panici, P., Mancuso, S., Neri, G., and Testa, J. R. (1995) Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas. Int. J. Cancer 64, 280-285.
61. Larue, L., and Bellacosa, A. (2005) Epithelial-mesenchymal transition in development and cancer: Role of phosphatidylinositol 3-kinase/AKT pathways. Oncogene 24, 7443-7454.
62. Duffy, M. J., Mullooly, M., O'Donovan, N., Sukor, S., Crown, J., Pierce, A., and McGowan, P. M. (2011) The ADAMs family of proteases: new biomarkers and therapeutic targets for cancer? Clin. Proteomics 8, 9.
63. Dinh, P., Harnett, P., Piccart-Gebhart, M. J., and Awada, A. (2008) New therapies for ovarian cancer: cytotoxics and molecularly targeted agents. Crit. Rev. Oncol. Hematol. 67, 103-112.
64. Glaysher, S., Bolton, L. M., Johnson, P., Atkey, N., Dyson, M., Torrance, C., and Cree, I. A. (2013) Targeting EGFR and PI3K pathways in ovarian cancer. Br. J. Cancer 109, 1786-1794.
65. Pruessmeyer, J., Hess, F. M., Alert, H., Groth, E., Pasqualon, T., Schwarz, N., Nyamoya, S., Kollert, J., van der Vorst, E., Donners, M., Martin, C., Uhlig, S., Saftig, P., Dreymueller, D., and Ludwig, A. (2014) Leukocytes require ADAM10 but not ADAM17 for their migration and inflammatory recruitment into the alveolar space. Blood 123, 4077-4088.
66. Haley, J., Tomar, S., Pulliam, N., Xiong, S., Perkins, S. M., Karpf, A. R., Mitra, S., Nephew, K. P., and Mitra, A. K. (2016) Functional characterization of a panel of high-grade serous ovarian cancer cell lines as representative experimental models of the disease. Oncotarget 7, 32810-32820.
67. Mishra, H. K., Long, C., Bahaie, N. S., and Walcheck, B. (2015) Regulation of CXCR2 expression and function by a disintegrin and metalloprotease- 17 (ADAM17). J. Leukoc. Biol. 97, 447-454.
68. Schneider, C. A., Rasband, W. S., and Eliceiri, K. W. (2012) NIH Image to Image J: 25 years of image analysis. Nat. Methods 9, 671-675.