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Published in: Clinical & Experimental Metastasis 5/2008

01-09-2008 | Research Paper

Single-cell tumor dormancy model of uveal melanoma

Authors: Patrick T. Logan, Bruno F. Fernandes, Sebastian Di Cesare, Jean-Claude A. Marshall, Shawn C. Maloney, Miguel N. Burnier Jr.

Published in: Clinical & Experimental Metastasis | Issue 5/2008

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Abstract

Background Ocular melanoma is easily treated by the removal of the eye or through plaque radiotherapy. However, after removal or control of the primary tumor, patients can develop fatal liver metastases up to 20 years later. It has been reported that difficulties in imaging single cells and the propensity for tumor cells to replicate rapidly in animal models account for the deficit of single-cell tumor dormancy models. Methods In this paper, we performed two animal experiments using green fluorescent-labeled uveal melanoma cells in nude mice. Cells were injected via tail-vein and the experiments ran 20 and 42 days, respectively. Labeled cells were imaged in vivo via skin-flap and epifluorescent microscopy. Results The first experiment exemplified the feasibility of a single-cell tumor dormancy model; cells were present in multiple organs post-injection, but persisted solely in the liver for the duration of the experiment. The second experiment, demonstrating the presence and viability of these single, metastatic seeds 6 weeks after injection. Conclusion Due to the inherent difficulties in establishing single-celled tumor dormancy models, few exist. In this paper, we have successfully developed a single-cell dormancy model of uveal melanoma, a disease that, in patients, epitomizes tumor dormancy. This model has the potential to reveal the mechanisms behind dormancy, identify patients at high risk for metastatic development, and develop new serum biomarkers for micrometastasis detection.
Literature
1.
go back to reference Egan KM, Seddon JM, Glynn RJ et al (1988) Epidemiologic aspects of uveal melanoma. Surv Ophthalmol 32(4):239–251PubMedCrossRef Egan KM, Seddon JM, Glynn RJ et al (1988) Epidemiologic aspects of uveal melanoma. Surv Ophthalmol 32(4):239–251PubMedCrossRef
2.
go back to reference De Potter P, Shields CL, Shields JA (1996) New treatment modalities for uveal melanoma. Curr Opin Ophthalmol 7(3):27–32PubMedCrossRef De Potter P, Shields CL, Shields JA (1996) New treatment modalities for uveal melanoma. Curr Opin Ophthalmol 7(3):27–32PubMedCrossRef
3.
go back to reference Singh AD, Topham A (2003) Survival rates with uveal melanoma in the United States: 1973–1997. Ophthalmology 110(5):962–965PubMedCrossRef Singh AD, Topham A (2003) Survival rates with uveal melanoma in the United States: 1973–1997. Ophthalmology 110(5):962–965PubMedCrossRef
4.
go back to reference Assessment of metastatic disease status at death in 435 patients with large choroidal melanoma in the Collaborative Ocular Melanoma Study (COMS) (2001) COMS report no. 15. Arch Ophthalmol 119(5):670–676 Assessment of metastatic disease status at death in 435 patients with large choroidal melanoma in the Collaborative Ocular Melanoma Study (COMS) (2001) COMS report no. 15. Arch Ophthalmol 119(5):670–676
5.
go back to reference Kujala E, Makitie T, Kivela T (2003) Very long-term prognosis of patients with malignant uveal melanoma. Invest Ophthalmol Vis Sci 44(11):4651–4659PubMedCrossRef Kujala E, Makitie T, Kivela T (2003) Very long-term prognosis of patients with malignant uveal melanoma. Invest Ophthalmol Vis Sci 44(11):4651–4659PubMedCrossRef
6.
go back to reference De Croock L, Verbraeken H (2002) Metastatic uveal melanoma: diagnosis and treatment. A literature review. Bull Soc Belge Ophtalmol 286:59–63 De Croock L, Verbraeken H (2002) Metastatic uveal melanoma: diagnosis and treatment. A literature review. Bull Soc Belge Ophtalmol 286:59–63
7.
go back to reference Bedikian AY (2006) Metastatic uveal melanoma therapy: current options. Int Ophthalmol Clin 46(1):151–156PubMedCrossRef Bedikian AY (2006) Metastatic uveal melanoma therapy: current options. Int Ophthalmol Clin 46(1):151–156PubMedCrossRef
8.
go back to reference Callejo SA, Antecka E, Blanco PL et al (2006) Identification of circulating malignant cells and its correlation with prognostic factors and treatment in uveal melanoma. A prospective longitudinal study. Eye 21(6):752–759PubMedCrossRef Callejo SA, Antecka E, Blanco PL et al (2006) Identification of circulating malignant cells and its correlation with prognostic factors and treatment in uveal melanoma. A prospective longitudinal study. Eye 21(6):752–759PubMedCrossRef
9.
go back to reference Diener-West M, Reynolds SM, Agugliaro DJ et al (2004) Screening for metastasis from choroidal melanoma: the Collaborative Ocular Melanoma Study Group Report 23. J Clin Oncol 22(12):2438–2444PubMedCrossRef Diener-West M, Reynolds SM, Agugliaro DJ et al (2004) Screening for metastasis from choroidal melanoma: the Collaborative Ocular Melanoma Study Group Report 23. J Clin Oncol 22(12):2438–2444PubMedCrossRef
10.
go back to reference Blanco PL, Marshall JC, Antecka E et al (2005) Characterization of ocular and metastatic uveal melanoma in an animal model. Invest Ophthalmol Vis Sci 46(12):4376–4382PubMedCrossRef Blanco PL, Marshall JC, Antecka E et al (2005) Characterization of ocular and metastatic uveal melanoma in an animal model. Invest Ophthalmol Vis Sci 46(12):4376–4382PubMedCrossRef
11.
go back to reference Notting IC, Buijs JT, Que I et al (2005) Whole-body bioluminescent imaging of human uveal melanoma in a new mouse model of local tumor growth and metastasis. Invest Ophthalmol Vis Sci 46(5):1581–1587PubMedCrossRef Notting IC, Buijs JT, Que I et al (2005) Whole-body bioluminescent imaging of human uveal melanoma in a new mouse model of local tumor growth and metastasis. Invest Ophthalmol Vis Sci 46(5):1581–1587PubMedCrossRef
12.
go back to reference Romer TJ, van Delft JL, de Wolff-Rouendaal D et al (1992) Hamster Greene melanoma implanted in the anterior chamber of a rabbit eye: a reliable tumor model? Ophthalmic Res 24(2):119–124PubMedCrossRef Romer TJ, van Delft JL, de Wolff-Rouendaal D et al (1992) Hamster Greene melanoma implanted in the anterior chamber of a rabbit eye: a reliable tumor model? Ophthalmic Res 24(2):119–124PubMedCrossRef
13.
go back to reference Marshall JC, Fernandes BF, Di Cesare S et al (2007) The use of a cyclooxygenase-2 inhibitor (Nepafenac) in an ocular and metastatic animal model of uveal melanoma. Carcinogenesis 28(9):2053–2058PubMedCrossRef Marshall JC, Fernandes BF, Di Cesare S et al (2007) The use of a cyclooxygenase-2 inhibitor (Nepafenac) in an ocular and metastatic animal model of uveal melanoma. Carcinogenesis 28(9):2053–2058PubMedCrossRef
14.
go back to reference Brackstone M, Townson JL, Chambers AF (2007) Tumour dormancy in breast cancer: an update. Breast Cancer Res 9(3):208PubMedCrossRef Brackstone M, Townson JL, Chambers AF (2007) Tumour dormancy in breast cancer: an update. Breast Cancer Res 9(3):208PubMedCrossRef
15.
go back to reference Bayko L, Rak J, Man S et al (1998) The dormant in vivo phenotype of early stage primary human melanoma: termination by overexpression of vascular endothelial growth factor. Angiogenesis 2(3):203–217PubMedCrossRef Bayko L, Rak J, Man S et al (1998) The dormant in vivo phenotype of early stage primary human melanoma: termination by overexpression of vascular endothelial growth factor. Angiogenesis 2(3):203–217PubMedCrossRef
16.
go back to reference Clark WH (1991) Tumour progression and the nature of cancer. Br J Cancer 64(4):631–644PubMed Clark WH (1991) Tumour progression and the nature of cancer. Br J Cancer 64(4):631–644PubMed
17.
go back to reference Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev 2(8):563–572 Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev 2(8):563–572
18.
go back to reference Luzzi KJ, MacDonald IC, Schmidt EE et al (1998) Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases. Am J Pathol 153(3):865–873PubMed Luzzi KJ, MacDonald IC, Schmidt EE et al (1998) Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases. Am J Pathol 153(3):865–873PubMed
19.
go back to reference Chambers AF, Naumov GN, Varghese HJ et al (2001) Critical steps in hematogenous metastasis: an overview. Surg Oncol Clin N Am 10(2):243–255, vii Chambers AF, Naumov GN, Varghese HJ et al (2001) Critical steps in hematogenous metastasis: an overview. Surg Oncol Clin N Am 10(2):243–255, vii
20.
go back to reference Townson JL, Chambers AF (2006) Dormancy of solitary metastatic cells. Cell cycle (Georgetown, Tex) 5(16):1744–1750 Townson JL, Chambers AF (2006) Dormancy of solitary metastatic cells. Cell cycle (Georgetown, Tex) 5(16):1744–1750
21.
go back to reference Marshall JC, Caissie AL, Callejo SA et al (2004) Cell proliferation profile of five human uveal melanoma cell lines of different metastatic potential. Pathobiology 71(5):241–245PubMedCrossRef Marshall JC, Caissie AL, Callejo SA et al (2004) Cell proliferation profile of five human uveal melanoma cell lines of different metastatic potential. Pathobiology 71(5):241–245PubMedCrossRef
22.
go back to reference De Waard-Siebinga I, Blom DJ, Griffioen M et al (1995) Establishment and characterization of an uveal-melanoma cell line. Int J Cancer 62(2):155–161PubMedCrossRef De Waard-Siebinga I, Blom DJ, Griffioen M et al (1995) Establishment and characterization of an uveal-melanoma cell line. Int J Cancer 62(2):155–161PubMedCrossRef
23.
go back to reference Skehan P, Storeng R, Scudiero D et al (1990) New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Canc Inst 82(13):1107–1112CrossRef Skehan P, Storeng R, Scudiero D et al (1990) New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Canc Inst 82(13):1107–1112CrossRef
24.
go back to reference Saraiva VS, Marshall JC, Cools-Lartigue J et al (2004) Cytotoxic effects of violacein in human uveal melanoma cell lines. Melanoma Res 14(5):421–424PubMedCrossRef Saraiva VS, Marshall JC, Cools-Lartigue J et al (2004) Cytotoxic effects of violacein in human uveal melanoma cell lines. Melanoma Res 14(5):421–424PubMedCrossRef
25.
go back to reference Naumov GN, Wilson SM, MacDonald IC et al (1999) Cellular expression of green fluorescent protein, coupled with high-resolution in vivo videomicroscopy, to monitor steps in tumor metastasis. J Cell Sci 112( Pt 12):1835–1842PubMed Naumov GN, Wilson SM, MacDonald IC et al (1999) Cellular expression of green fluorescent protein, coupled with high-resolution in vivo videomicroscopy, to monitor steps in tumor metastasis. J Cell Sci 112( Pt 12):1835–1842PubMed
26.
go back to reference Eskelin S, Pyrhonen S, Summanen P et al (2000) Tumor doubling times in metastatic malignant melanoma of the uvea: tumor progression before and after treatment. Ophthalmology 107(8):1443–1449PubMedCrossRef Eskelin S, Pyrhonen S, Summanen P et al (2000) Tumor doubling times in metastatic malignant melanoma of the uvea: tumor progression before and after treatment. Ophthalmology 107(8):1443–1449PubMedCrossRef
27.
go back to reference Economou MA, All-Ericsson C, Bykov V et al (2005) Receptors for the liver synthesized growth factors IGF-1 and HGF/SF in uveal melanoma: intercorrelation and prognostic implications. Invest Ophthalmol Vis Sci 46(12):4372–4375PubMedCrossRef Economou MA, All-Ericsson C, Bykov V et al (2005) Receptors for the liver synthesized growth factors IGF-1 and HGF/SF in uveal melanoma: intercorrelation and prognostic implications. Invest Ophthalmol Vis Sci 46(12):4372–4375PubMedCrossRef
28.
go back to reference Hurks HM, Metzelaar-Blok JA, Barthen ER et al (2000) Expression of epidermal growth factor receptor: risk factor in uveal melanoma. Invest Ophthalmol Vis Sci 41(8):2023–2027PubMed Hurks HM, Metzelaar-Blok JA, Barthen ER et al (2000) Expression of epidermal growth factor receptor: risk factor in uveal melanoma. Invest Ophthalmol Vis Sci 41(8):2023–2027PubMed
29.
go back to reference Paget S (1989) The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev 8(2):98–101PubMed Paget S (1989) The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev 8(2):98–101PubMed
30.
go back to reference Grahn JC, Reilly DA, Nuccitelli RL et al (2003) Melanocytes do not migrate directionally in physiological DC electric fields. Wound Repair Regen 11(1):64–70PubMedCrossRef Grahn JC, Reilly DA, Nuccitelli RL et al (2003) Melanocytes do not migrate directionally in physiological DC electric fields. Wound Repair Regen 11(1):64–70PubMedCrossRef
31.
go back to reference Goldberg SF, Harms JF, Quon K et al (1999) Metastasis-suppressed C8161 melanoma cells arrest in lung but fail to proliferate. Clin Exp Metastasis 17(7):601–607PubMedCrossRef Goldberg SF, Harms JF, Quon K et al (1999) Metastasis-suppressed C8161 melanoma cells arrest in lung but fail to proliferate. Clin Exp Metastasis 17(7):601–607PubMedCrossRef
32.
go back to reference Mitsiades CS, Mitsiades NS, Bronson RT et al (2003) Fluorescence imaging of multiple myeloma cells in a clinically relevant SCID/NOD in vivo model: biologic and clinical implications. Cancer Res 63(20):6689–6696PubMed Mitsiades CS, Mitsiades NS, Bronson RT et al (2003) Fluorescence imaging of multiple myeloma cells in a clinically relevant SCID/NOD in vivo model: biologic and clinical implications. Cancer Res 63(20):6689–6696PubMed
33.
go back to reference Naumov GN, Townson JL, MacDonald IC et al (2003) Ineffectiveness of doxorubicin treatment on solitary dormant mammary carcinoma cells or late-developing metastases. Breast Cancer Res Treat 82(3):199–206PubMedCrossRef Naumov GN, Townson JL, MacDonald IC et al (2003) Ineffectiveness of doxorubicin treatment on solitary dormant mammary carcinoma cells or late-developing metastases. Breast Cancer Res Treat 82(3):199–206PubMedCrossRef
34.
go back to reference Fidler IJ (2003) The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev 3(6):453–458 Fidler IJ (2003) The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev 3(6):453–458
35.
go back to reference Contag PR, Olomu IN, Stevenson DK et al (1998) Bioluminescent indicators in living mammals. Nat Med 4(2):245–247PubMedCrossRef Contag PR, Olomu IN, Stevenson DK et al (1998) Bioluminescent indicators in living mammals. Nat Med 4(2):245–247PubMedCrossRef
36.
go back to reference Heyn C, Ronald JA, Ramadan SS et al (2006) In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain. Magn Reson Med 56(5):1001–1010PubMedCrossRef Heyn C, Ronald JA, Ramadan SS et al (2006) In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain. Magn Reson Med 56(5):1001–1010PubMedCrossRef
Metadata
Title
Single-cell tumor dormancy model of uveal melanoma
Authors
Patrick T. Logan
Bruno F. Fernandes
Sebastian Di Cesare
Jean-Claude A. Marshall
Shawn C. Maloney
Miguel N. Burnier Jr.
Publication date
01-09-2008
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 5/2008
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-008-9158-2

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