Summary
According to animal experiments, metastasis to a particular organ depends on the phenotype of the tumor cells. Widespread metastatic dissemination including internal organs would therefore, at least in part, depend on the capacity of tumor cells to modulate, resulting in increased phenotypic heterogeneity. We found evidence for this assumption in human melanoma by phenotyping metastases (mainly cutaneous/subcutaneous) from 59 patients by the use of six monoclonal antibodies. Interlesional antigenic heterogeneity was present in 22/33 (67%) patients with disseminated metastases including at least one internal organ, but only in 4/26 (15%) patients whose metastases were restricted to skin and/or skin-draining lymph nodes (P≤-0.01). Chemotherapy cannot be the main reason for interlesional phenotypic heterogeneity, as seen by comparison of treated and untreated patients. Aneuploid melanoma metastases, as an indication for instability on the chromosomal level, were found in the majority of patients (84%) regardless of their clinical situation. Widespread disease was significantly related to the loss of the cytoplasmatic antigen K-1-2 and to the expression of the 130-kDa membrane antigen A-1-43.
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Abbreviations
- mAb:
-
monoclonal antibody
References
Albino AP, Lloyd KO, Houghton AN, Oettgen HF, Old LJ (1981) Heterogeneity in surface antigen and glycoprotein expression of cell lines derived from different melanoma metastases of the same patient. Implications for the study of tumor antigens. J Exp Med 154:1764–1778
Bröcker EB, Suter L, Sorg C (1984) HLA-DR antigen expression in primary melanomas of the skin. J Invest Dermatol 82:244–247
Bröcker EB, Suter L, Brüggen J, Ruiter DJ, Macher E, Sorg C (1985) Phenotypic dynamics of tumor progression in human malignant melanoma. Int J Cancer 36:29–35
Brüggen J, Bröcker EB, Suter L, Redmann K, Sorg C (1984) The expression of tumor-associated antigens in primary and metastatic human malignant melanoma. Behring Inst Mitt 74:19–22
Bystryn JC, Bernstein P, Liu P, Valentine F (1985) Immunophenotype of human melanoma cells in different metastases. Cancer Res 45:5603–5607
Duinen SG van, Ruiter DJ, Bröcker EB, van derVelde EA, Sorg C, Welvaart K, Ferrone S (1988) Level of HLA antigens in locoregional metastases and clinical course of the disease in patients with melanoma. Cancer Res 48:1019–1025
Fidler IJ, Hart IR (1982) Biological diversity in metastatic neoplasms: origins and implications. Science 217:998–1003
Hart IR, Fidler IJ (1980) Role of organ selectivity in the determination of metastatic patterns of B16 melanoma. Cancer Res 40:2281–2287
Heppner GH (1984) Tumor heterogeneity. Cancer Res 44:2259–2265
Holzmann B, Bröcker EB, Lehmann JM, Ruiter DJ, Sorg C, Riethmüller G, Johnson JP (1987) Tumor progression in human malignant melanoma: five stages defined by their antigenic phenotypes. Int J Cancer 39:466–471
Natali PG, Cavaliere R, Bigotti A, Nicotra MR, Russo C, Ng AK, Giacomini P, Ferrone S (1983) Antigenic heterogeneity of surgically removed primary and autologous metastatic human melanoma lesions. J Immunol 130:1462–1466
Natali PG, Bigotti A, Cavaliere R, Liao SK, Taniguchi M, Matsui M, Ferrone S (1985) Heterogeneos expression of melanomaassociated antigens and HLA antigens by primary and multiple metastatic lesions removed from patients with melanoma. Cancer Res 45:2883–2889
Nicolson GL, Winkelhake JL (1975) Organ specificity of bloodborne tumour metastasis determined by cell adhesion? Nature 255:230–232
Nowell PC (1976) The clonal evolution of tumor cell pupulations. Acquired genetic lability permits stepwise selection of variant sublines and underlies tumor progression Science 194:23–28
Nowell PC (1986) Mechanisms of tumor progression. Cancer Res 46:2203–2207
Poste G, Fidler IJ (1980) The pathogenesis of cancer metastasis. Nature 283:139–146
Poste G, Greig R, Tzeng J, Koestler T, Corwin S (1984) Interactions between tumor cell subpopulations in malignant tumors. In: Nicolson GL, Milas L (eds) Cancer invasion and metastasis. Biologic and therapeutic aspects. Raven, New York, pp 223–243
Ruiter DJ, van Duinen SG, Warnaar SO (1984) Immunohistopathological aspects of cutaneous melanoma and precursor lesions. In: Ruiter DJ, Welvaart K, Ferrone S (eds), Cutaneous melanoma and precursor lesions, Nijhoff, Boston, Dordrecht, Lancaster, pp 112–125
Schirrmacher V, Bosslet K, Shantz G, Clauer K, Hübsch D (1979) Tumor metastases and cell-mediated immunity in a model system in DBA/2 mice. IV. Antigenic differences between metastasizing variant and the parental tumor line revealed by cytotoxic T lymphocytes. Int J Cancer 23:245–252
Sorg C, Bröcker EB, Zwadlo G, Redmann K, Feige U, Ax W, Feller AC (1985) A monoclonal antibody to a formaldehyde-resistent epitope on the nonpolymorphic constant part of the HLA-DR antigens. Transplantation 39:90–93
Stenzinger W, Suter L, Schumann J (1984) DNA aneuploidy in congenital melanocytic nevi: Suggestive evidence for premalignant changes. J Invest Dermatol 82:569–572
Suter L, Bröcker EB, Brüggen J, Ruiter DJ, Sorg C (1983) Heterogeneity of primary and metastatic human malignant melanoma as detected with monoclonal antibodies in cryostat sections of biopsies. Cancer Immunol Immunother 16:53–58
Suter L, Brüggen J, Bröcker EB, Sorg C (1985) A tumor associated antigen expressed in melanoma cells with lower malignant potential. Int J Cancer 35:787–791
Yogeeswaran G, Stein BS, Sebastian H (1978) Altered cell surface organization of gangliosides and sialylglycoproteins of mouse metastatic melanoma variant lines selected in vivo for enhanced lung implantation. Cancer Res 38:1336–1344
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Dedicated to Professor Dr. E. Macher on the occasion of his 65th birthday
This work was supported by the Deutsche Krebshilfe (grant M 55/85/Su 1) and the Deutsche Forschungsgemeinschaft (grant Br 527/3-2)
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Suter, L., Bröcker, EB., Ostmeier, H. et al. Metastatic human melanoma. J Cancer Res Clin Oncol 115, 459–464 (1989). https://doi.org/10.1007/BF00393338
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DOI: https://doi.org/10.1007/BF00393338