{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T20:10:14Z","timestamp":1771963814110,"version":"3.50.1"},"reference-count":90,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:00:00Z","timestamp":1720483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chinese Scholarship Fund","award":["CSC 2024"],"award-info":[{"award-number":["CSC 2024"]}]},{"name":"Chinese Scholarship Fund","award":["2021-043"],"award-info":[{"award-number":["2021-043"]}]},{"name":"Dr. Rolf M. Schwiete Stiftung","award":["CSC 2024"],"award-info":[{"award-number":["CSC 2024"]}]},{"name":"Dr. Rolf M. Schwiete Stiftung","award":["2021-043"],"award-info":[{"award-number":["2021-043"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Uveal melanoma (UM) is the most common intraocular tumor in adults, and nearly 50% of patients develop metastatic disease with a high mortality rate. Therefore, the development of relevant preclinical in vivo models that accurately recapitulate the metastatic cascade is crucial. We exploited the chick embryo chorioallantoic membrane (CAM) xenograft model to quantify both experimental and spontaneous metastasis by qPCR analysis. Our study found that the transplanted UM cells spread predominantly and early in the liver, reflecting the primary site of metastasis in patients. Visible signs of pigmented metastasis were observed in the eyes, liver, and distal CAM. Lung metastases occurred rarely and brain metastases progressed more slowly. However, UM cell types of different origins and genetic profiles caused an individual spectrum of organ metastases. Metastasis to multiple organs, including the liver, was often associated with risk factors such as high proliferation rate, hyperpigmentation, and epithelioid cell type. The severity of liver metastasis was related to the hepatic metastatic origin and chromosome 8 abnormalities rather than monosomy 3 and BAP1 deficiency. The presented CAM xenograft model may prove useful to study the metastatic potential of patients or to test individualized therapeutic options for metastasis in different organs.<\/jats:p>","DOI":"10.3390\/cells13141169","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T15:27:20Z","timestamp":1720538840000},"page":"1169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Chick Chorioallantoic Membrane as a Xenograft Model for the Quantitative Analysis of Uveal Melanoma Metastasis in Multiple Organs"],"prefix":"10.3390","volume":"13","author":[{"given":"Hongtao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theodora","family":"Tsimpaki","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4067-2795","authenticated-orcid":false,"given":"Ralitsa","family":"Anastasova","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0180-1112","authenticated-orcid":false,"given":"Nikolaos E.","family":"Bechrakis","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7868-5167","authenticated-orcid":false,"given":"Miltiadis","family":"Fiorentzis","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Utta","family":"Berchner-Pfannschmidt","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"500","DOI":"10.5858\/arpa.2019-0561-RA","article-title":"The 2018 World Health Organization Classification of Cutaneous, Mucosal, and Uveal Melanoma: Detailed Analysis of 9 Distinct Subtypes Defined by Their Evolutionary Pathway","volume":"144","author":"Elder","year":"2020","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.ajo.2016.06.002","article-title":"Validation of a Prognostic Staging for Metastatic Uveal Melanoma: A Collaborative Study of the European Ophthalmic Oncology Group","volume":"168","author":"Kivela","year":"2016","journal-title":"Am. J. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1016\/j.ophtha.2011.01.040","article-title":"Uveal melanoma: Trends in incidence, treatment, and survival","volume":"118","author":"Singh","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1016\/j.ophtha.2007.01.032","article-title":"Incidence of uveal melanoma in Europe","volume":"114","author":"Virgili","year":"2007","journal-title":"Ophthalmology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4651","DOI":"10.1167\/iovs.03-0538","article-title":"Very long-term prognosis of patients with malignant uveal melanoma","volume":"44","author":"Kujala","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3282","DOI":"10.1167\/iovs.03-0081","article-title":"Uveal melanoma survival in Sweden from 1960 to 1998","volume":"44","author":"Bergman","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1001\/archopht.123.12.1639","article-title":"Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: Collaborative Ocular Melanoma Study Group Report No. 26","volume":"123","author":"Reynolds","year":"2005","journal-title":"Arch. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101041","DOI":"10.1016\/j.preteyeres.2022.101041","article-title":"Metastatic uveal melanoma: The final frontier","volume":"90","author":"Rantala","year":"2022","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"382","DOI":"10.14694\/EdBook_AM.2013.33.382","article-title":"Surveillance options for patients with uveal melanoma following definitive management","volume":"33","author":"Francis","year":"2013","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1755-3768.2009.01617.x","article-title":"Circulating melanoma cells in peripheral blood of patients with uveal melanoma before and after different therapies and association with prognostic parameters: A pilot study","volume":"89","author":"Suesskind","year":"2011","journal-title":"Acta Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1001\/archopht.1996.01100130103030","article-title":"Metastatic ocular and cutaneous melanoma: A comparison of patient characteristics and prognosis","volume":"114","author":"Albert","year":"1996","journal-title":"Arch. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1136\/bjophthalmol-2012-302323","article-title":"MRI in the detection of hepatic metastases from high-risk uveal melanoma: A prospective study in 188 patients","volume":"97","author":"Marshall","year":"2013","journal-title":"Br. J. Ophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1002\/jso.24984","article-title":"Hepatic artery infusion of melphalan in patients with liver metastases from ocular melanoma","volume":"117","author":"Boone","year":"2018","journal-title":"J. Surg. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lamas, N.J., Martel, A., Nahon-Esteve, S., Goffinet, S., Macocco, A., Bertolotto, C., Lassalle, S., and Hofman, P. (2022). Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances abd Future Directions. Cancers, 14.","DOI":"10.3390\/cancers14010096"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1002\/cjp2.105","article-title":"Replacement and desmoplastic histopathological growth patterns: A pilot study of prediction of outcome in patients with uveal melanoma liver metastases","volume":"4","author":"Barnhill","year":"2018","journal-title":"J. Pathol. Clin. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1002\/1097-0142(19951101)76:9<1665::AID-CNCR2820760925>3.0.CO;2-J","article-title":"Treatment of uveal melanoma metastatic to the liver: A review of the M. D. Anderson Cancer Center experience and prognostic factors","volume":"76","author":"Bedikian","year":"1995","journal-title":"Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.humpath.2016.07.012","article-title":"Metastatic ocular melanoma to the liver exhibits infiltrative and nodular growth patterns","volume":"57","author":"Grossniklaus","year":"2016","journal-title":"Hum. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1111\/pcmr.12433","article-title":"Insights into genetic alterations of liver metastases from uveal melanoma","volume":"29","author":"McCarthy","year":"2016","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1016\/S0161-6420(00)00182-2","article-title":"Tumor doubling times in metastatic malignant melanoma of the uvea: Tumor progression before and after treatment","volume":"107","author":"Eskelin","year":"2000","journal-title":"Ophthalmology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1136\/bjo.2008.153684","article-title":"Long-term survival of uveal melanoma patients after surgery for liver metastases","volume":"93","author":"Frenkel","year":"2009","journal-title":"Br. J. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1136\/bjophthalmol-2020-317949","article-title":"Patients presenting with metastases: Stage IV uveal melanoma, an international study","volume":"106","author":"Garg","year":"2022","journal-title":"Br. J. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1001\/archophthalmol.2009.401","article-title":"Hepatic Abnormalities Identified on Abdominal Computed Tomography at Diagnosis of Uveal Melanoma","volume":"128","author":"Feinstein","year":"2010","journal-title":"Arch. Ophthalmol.-Chic."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"236","DOI":"10.5301\/ejo.5000049","article-title":"Initial PET\/CT staging for choroidal melanoma: AJCC correlation and second nonocular primaries in 333 patients","volume":"22","author":"Freton","year":"2012","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1136\/bjophthalmol-2020-318658","article-title":"Presumed incipient choroidal melanoma: Proposed diagnostic criteria and management","volume":"107","author":"Jouhi","year":"2023","journal-title":"Br. J. Ophthalmol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.jcjo.2012.03.038","article-title":"Uveal melanoma prognostication: From lesion size and cell type to molecular class","volume":"47","author":"Gill","year":"2012","journal-title":"Can. J. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/S0002-9394(14)77914-0","article-title":"Modifications of Callender\u2019s classification of uveal melanoma at the Armed Forces Institute of Pathology","volume":"96","author":"McLean","year":"1983","journal-title":"Am. J. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1016\/S0161-6420(93)31470-3","article-title":"The prognostic value of tumor blood vessel morphology in primary uveal melanoma","volume":"100","author":"Folberg","year":"1993","journal-title":"Ophthalmology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"14","DOI":"10.17116\/patol20218304114","article-title":"The prognostic value of uveal melanoma cell type","volume":"83","author":"Yarovaya","year":"2021","journal-title":"Arkh Patol."},{"key":"ref_29","first-page":"745","article-title":"Histopathology, morphometry, and nuclear DNA content of iris melanocytic lesions","volume":"36","author":"Grossniklaus","year":"1995","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/S0161-6420(94)31184-5","article-title":"Mean of the ten largest nucleoli, microcirculation architecture, and prognosis of ciliochoroidal melanomas","volume":"101","author":"Rummelt","year":"1994","journal-title":"Ophthalmology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/S0002-9394(14)77877-8","article-title":"The value of nucleolar organizer regions in uveal melanoma. The Collaborative Ocular Melanoma Study Group","volume":"110","author":"Marcus","year":"1990","journal-title":"Am. J. Ophthalmol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/S0161-6420(97)30234-6","article-title":"Uveal melanoma. Comparison of the prognostic value of fibrovascular loops, mean of the ten largest nucleoli, cell type, and tumor size","volume":"104","author":"McLean","year":"1997","journal-title":"Ophthalmology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8923","DOI":"10.1038\/s41598-021-88390-6","article-title":"Estimation of the timing of BAP1 mutation in uveal melanoma progression","volume":"11","author":"Uner","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/ijc.11558","article-title":"Dissecting karyotypic patterns in malignant melanomas: Temporal clustering of losses and gains in melanoma karyotypic evolution","volume":"108","author":"Hoglund","year":"2004","journal-title":"Int. J. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3703","DOI":"10.1167\/iovs.06-0101","article-title":"Clinical and cytogenetic analyses in uveal melanoma","volume":"47","author":"Kilic","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/eye.2012.255","article-title":"Molecular pathology of uveal melanoma","volume":"27","author":"Coupland","year":"2013","journal-title":"Eye"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/nature07586","article-title":"Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi","volume":"457","author":"Bezrookove","year":"2009","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1001\/jamaophthalmol.2015.1119","article-title":"Clinical Characteristics of Uveal Melanoma in Patients With Germline BAP1 Mutations","volume":"133","author":"Gupta","year":"2015","journal-title":"JAMA Ophthalmol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Vivet-Noguer, R., Tarin, M., Roman-Roman, S., and Alsafadi, S. (2019). Emerging Therapeutic Opportunities Based on Current Knowledge of Uveal Melanoma Biology. Cancers, 11.","DOI":"10.3390\/cancers11071019"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1038\/ng.2674","article-title":"Exome sequencing identifies recurrent somatic mutations in EIF1AX and SF3B1 in uveal melanoma with disomy 3","volume":"45","author":"Martin","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1038\/bjc.2012.54","article-title":"Prognostic significance of chromosome 3 alterations determined by microsatellite analysis in uveal melanoma: A long-term follow-up study","volume":"106","author":"Thomas","year":"2012","journal-title":"Br. J. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1136\/bjo.85.12.1440","article-title":"Prediction of prognosis in patients with uveal melanoma using fluorescence in situ hybridisation","volume":"85","author":"Patel","year":"2001","journal-title":"Br. J. Ophthalmol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"100800","DOI":"10.1016\/j.preteyeres.2019.100800","article-title":"Uveal melanoma: Towards a molecular understanding","volume":"75","author":"Smit","year":"2020","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.ccell.2017.07.003","article-title":"Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma","volume":"32","author":"Robertson","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Bakhoum, M.F., and Esmaeli, B. (2019). Molecular Characteristics of Uveal Melanoma: Insights from the Cancer Genome Atlas (TCGA) Project. Cancers, 11.","DOI":"10.3390\/cancers11081061"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4624","DOI":"10.18632\/oncotarget.6614","article-title":"Deep sequencing of uveal melanoma identifies a recurrent mutation in PLCB4","volume":"7","author":"Johansson","year":"2016","journal-title":"Oncotarget"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/ng.3549","article-title":"Recurrent activating mutations of G-protein-coupled receptor CYSLTR2 in uveal melanoma","volume":"48","author":"Moore","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1111\/pcmr.12700","article-title":"Uveal melanoma driver mutations in GNAQ\/11 yield numerous changes in melanocyte biology","volume":"31","author":"Perez","year":"2018","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1038\/s41588-019-0440-9","article-title":"The genetic evolution of metastatic uveal melanoma","volume":"51","author":"Shain","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1056\/NEJMoa1000584","article-title":"Mutations in GNA11 in uveal melanoma","volume":"363","author":"Griewank","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7205","DOI":"10.1158\/0008-5472.CAN-04-1750","article-title":"Gene expression profiling in uveal melanoma reveals two molecular classes and predicts metastatic death","volume":"64","author":"Onken","year":"2004","journal-title":"Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1126\/science.1194472","article-title":"Frequent mutation of BAP1 in metastasizing uveal melanomas","volume":"330","author":"Harbour","year":"2010","journal-title":"Science"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e31250","DOI":"10.7554\/eLife.31250","article-title":"eIF1A residues implicated in cancer stabilize translation preinitiation complexes and favor suboptimal initiation sites in yeast","volume":"6","author":"Zhou","year":"2017","journal-title":"eLife"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.ophtha.2016.01.023","article-title":"Uveal Melanomas with SF3B1 Mutations: A Distinct Subclass Associated with Late-Onset Metastases","volume":"123","author":"Yavuzyigitoglu","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Teixido, C., Castillo, P., Martinez-Vila, C., Arance, A., and Alos, L. (2021). Molecular Markers and Targets in Melanoma. Cells, 10.","DOI":"10.3390\/cells10092320"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.reprotox.2016.11.004","article-title":"The chick embryo chorioallantoic membrane (CAM) assay","volume":"70","author":"Ribatti","year":"2017","journal-title":"Reprod. Toxicol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"112510","DOI":"10.1016\/j.yexcr.2021.112510","article-title":"The CAM assay in the study of the metastatic process","volume":"400","author":"Ribatti","year":"2021","journal-title":"Exp. Cell Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.yexcr.2014.06.010","article-title":"The chick embryo chorioallantoic membrane as a model for tumor biology","volume":"328","author":"Ribatti","year":"2014","journal-title":"Exp. Cell Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1159\/000370151","article-title":"Use of the Chick Embryo Model in Uveal Melanoma","volume":"1","author":"Kalirai","year":"2015","journal-title":"Ocul. Oncol. Pathol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Ionita, I., Malita, D., Dehelean, C., Olteanu, E., Marcovici, I., Geamantan, A., Chiriac, S., Roman, A., and Radu, D. (2023). Experimental Models for Rare Melanoma Research-The Niche That Needs to Be Addressed. Bioengineering, 10.","DOI":"10.3390\/bioengineering10060673"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Tsimpaki, T., Anastasova, R., Liu, H., Seitz, B., Bechrakis, N.E., Berchner-Pfannschmidt, U., Kraemer, M.M., and Fiorentzis, M. (2024). Calcium Electroporation versus Electrochemotherapy with Bleomycin in an In Vivo CAM-Based Uveal Melanoma Xenograft Model. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25020938"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Tsimpaki, T., Bechrakis, N.E., Seitz, B., Kraemer, M.M., Liu, H., Dalbah, S., Sokolenko, E., Berchner-Pfannschmidt, U., and Fiorentzis, M. (2023). Chick Chorioallantoic Membrane as a Patient-Derived Xenograft Model for Uveal Melanoma: Imaging Modalities for Growth and Vascular Evaluation. Cancers, 15.","DOI":"10.3390\/cancers15051436"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/ijc.2910620208","article-title":"Establishment and characterization of an uveal-melanoma cell line","volume":"62","author":"Blom","year":"1995","journal-title":"Int. J. Cancer"},{"key":"ref_64","first-page":"T5","article-title":"Uveal Melanoma Cell Lines: Where Do They Come From? (An American Ophthalmological Society Thesis)","volume":"114","author":"Jager","year":"2016","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1002\/(SICI)1097-0215(19971114)73:4<470::AID-IJC3>3.0.CO;2-X","article-title":"Melanomas that develop within the eye inhibit lymphocyte proliferation","volume":"73","author":"Verbik","year":"1997","journal-title":"Int. J. Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4660","DOI":"10.1167\/iovs.03-0151","article-title":"Dose fractionation effects in primary and metastatic human uveal melanoma cell lines","volume":"44","author":"Kilic","year":"2003","journal-title":"Investg. Ophthalmol. Vis. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1016\/j.molonc.2014.06.004","article-title":"Establishment of novel cell lines recapitulating the genetic landscape of uveal melanoma and preclinical validation of mTOR as a therapeutic target","volume":"8","author":"Nemati","year":"2014","journal-title":"Mol. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1159\/000201566","article-title":"Novel cell lines derived by long-term culture of primary uveal melanomas","volume":"223","author":"Nareyeck","year":"2009","journal-title":"Ophthalmologica"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1111\/j.1755-148X.2012.00971.x","article-title":"Genetic and molecular characterization of uveal melanoma cell lines","volume":"25","author":"Griewank","year":"2012","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Mergener, S., Siveke, J.T., and Pena-Llopis, S. (2021). Monosomy 3 Is Linked to Resistance to MEK Inhibitors in Uveal Melanoma. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136727"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Sokolenko, E.A., Berchner-Pfannschmidt, U., Ting, S.C., Schmid, K.W., Bechrakis, N.E., Seitz, B., Tsimpaki, T., Kraemer, M.M., and Fiorentzis, M. (2021). Optimisation of the Chicken Chorioallantoic Membrane Assay in Uveal Melanoma Research. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14010013"},{"key":"ref_72","first-page":"7083","article-title":"A quantitative analysis of rate-limiting steps in the metastatic cascade using human-specific real-time polymerase chain reaction","volume":"62","author":"Zijlstra","year":"2002","journal-title":"Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"van den Bosch, Q.C.C., de Klein, A., Verdijk, R.M., Kilic, E., Brosens, E., and Rotterdam Ocular Melanoma Study, G. (2024). Uveal melanoma modeling in mice and zebrafish. Biochim. Biophys. Acta Rev. Cancer, 1879.","DOI":"10.1016\/j.bbcan.2023.189055"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1158\/0008-5472.CAN-10-0605","article-title":"High PTP4A3 phosphatase expression correlates with metastatic risk in uveal melanoma patients","volume":"71","author":"Laurent","year":"2011","journal-title":"Cancer Res."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Merlos Rodrigo, M.A., Casar, B., Michalkova, H., Jimenez Jimenez, A.M., Heger, Z., and Adam, V. (2021). Extending the Applicability of In Ovo and Ex Ovo Chicken Chorioallantoic Membrane Assays to Study Cytostatic Activity in Neuroblastoma Cells. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.707366"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1080\/02713683.2022.2152055","article-title":"Using the Chick Embryo Model to Examine the Effects of Hypoxia Pre-conditioning of Uveal Melanoma Cells on Tumor Growth and Metastasis","volume":"48","author":"Draper","year":"2023","journal-title":"Curr. Eye Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"6612","DOI":"10.1167\/iovs.14-15202","article-title":"Modeling of human uveal melanoma in zebrafish xenograft embryos","volume":"55","author":"Burrello","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Yavuzyigitoglu, S., Tang, M.C.Y., Jansen, M., Geul, K.W., Dwarkasing, R.S., Vaarwater, J., Drabarek, W., Verdijk, R.M., Paridaens, D., and Naus, N.C. (2021). Radiological Patterns of Uveal Melanoma Liver Metastases in Correlation to Genetic Status. Cancers, 13.","DOI":"10.3390\/cancers13215316"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"100413","DOI":"10.1016\/j.xops.2023.100413","article-title":"8q Gain Has No Additional Predictive Value in SF3B1(MUT) Uveal Melanoma but Is Predictive for a Worse Prognosis in Patients with BAP1(MUT) Uveal Melanoma","volume":"4","author":"Nguyen","year":"2024","journal-title":"Ophthalmol. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1136\/bjo-2023-323816","article-title":"Ki67 is a better marker than PRAME in risk stratification of BAP1-positive and BAP1-loss uveal melanomas","volume":"108","author":"Donizy","year":"2023","journal-title":"Br. J. Ophthalmol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Tanaka, R., Terai, M., Londin, E., and Sato, T. (2021). The Role of HGF\/MET Signaling in Metastatic Uveal Melanoma. Cancers, 13.","DOI":"10.3390\/cancers13215457"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1158\/1541-7786.MCR-21-0526","article-title":"Uveal Melanoma Exosomes Induce a Prometastatic Microenvironment through Macrophage Migration Inhibitory Factor","volume":"20","author":"Ambrosini","year":"2022","journal-title":"Mol. Cancer Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"100297","DOI":"10.1016\/j.xops.2023.100297","article-title":"Increased Histological Tumor Pigmentation in Uveal Melanoma Is Related to Eye Color and Loss of Chromosome 3\/BAP1","volume":"3","author":"Gelmi","year":"2023","journal-title":"Ophthalmol. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.semcancer.2020.05.003","article-title":"Uveal melanoma pathobiology: Metastasis to the liver","volume":"71","author":"Bustamante","year":"2021","journal-title":"Semin. Cancer Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"7","DOI":"10.21037\/aes-21-30","article-title":"Animal Models of Uveal Melanoma","volume":"7","author":"Uner","year":"2022","journal-title":"Ann. Eye Sci."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Matatall, K.A., Agapova, O.A., Onken, M.D., Worley, L.A., Bowcock, A.M., and Harbour, J.W. (2013). BAP1 deficiency causes loss of melanocytic cell identity in uveal melanoma. BMC Cancer, 13.","DOI":"10.1186\/1471-2407-13-371"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1016\/j.celrep.2018.01.081","article-title":"GNA11 Q209L Mouse Model Reveals RasGRP3 as an Essential Signaling Node in Uveal Melanoma","volume":"22","author":"Moore","year":"2018","journal-title":"Cell Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1002\/1878-0261.13128","article-title":"Co-occurrence of BAP1 and SF3B1 mutations in uveal melanoma induces cellular senescence","volume":"16","author":"Yu","year":"2022","journal-title":"Mol. Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1038\/s41467-024-46906-4","article-title":"Uveal melanoma immunogenomics predict immunotherapy resistance and susceptibility","volume":"15","author":"Bhaskarla","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"De Lange, M.J., Nell, R.J., and van der Velden, P.A. (2021). Scientific and clinical implications of genetic and cellular heterogeneity in uveal melanoma. Mol. Biomed., 2.","DOI":"10.1186\/s43556-021-00048-x"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/14\/1169\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:12:20Z","timestamp":1760109140000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/14\/1169"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,9]]},"references-count":90,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["cells13141169"],"URL":"https:\/\/doi.org\/10.3390\/cells13141169","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,9]]}}}