Abstract
Mouse and human melanoma cells metastatic to the brain express degradative enzyme activities that are used for invasion of brain basement membrane and parenchyma. Compared to poorly metastatic or lung- or ovary-metastatic murine melanoma lines, the brain-metastatic sublines secreted higher levels of a variety of degradative enzymes. Brain-metastatic murine and human melanoma cells also degraded subendothelial basement membrane and reconstituted basement membrane at rates higher than other metastatic melanoma cells. In some cases these degradative activities in mouse and human melanoma cells can be induced by paracrine factors known to be present in the brain parenchyma, such as nerve growth factor (NGF). NGF stimulates the expression of degradative enzymes, such as the endo-Β-glucuronidase heparanase, that are important in basement membrane penetration but this factor does not stimulate melanoma cell growth. The growth of brain-metastasizing melanoma cells appears to be stimulated by other paracrine growth factors, such as paracrine transferrin. Melanoma cells metastatic to brain express higher numbers of transferrin receptors and respond and proliferate at lower concentrations of transferrin than do melanoma cells metastatic to other sites or poorly metastatic melanoma cells. The results suggest that degradation and invasion of brain basement membrane and responses to paracrine neurotrophins and paracrine transferrins are important properties in brain metastasis of murine and human malignant melanoma cells.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Liotta LA, Rao CN, Wewer UM: Biochemical interactions of tumor cells with the basement membrane. Annu Rev Biochem 55: 1037–1057, 1986
Nicolson GL: Cancer metastasis: tumor cell and host organ properties important in colonization of specific secondary sites. Biochim Biophys Acta 948: 175–224, 1988
Nicolson GL: Tumor and host molecules important in organ preference of metastasis. Semin Cancer Biol 2: 143–154, 1991
Nicolson GL: Paracrine and autocrine growth mechanisms in tumor metastasis to specific sites with particular emphasis on brain and lung metastasis. Cancer Metastasis Rev. 12: 325–343, 1993
Sugarbaker EV: Patterns of metastasis in human malignancies. Cancer Biol Rev 2: 235–278, 1983
Paget S: The distribution of secondary growths in cancer of the breast. Lancet 1: 571–573, 1889
Steck PA, Nicolson GL: Metastases to the central nervous system. In: Levine A, Schmidek H (eds) Molecular Genetics of Nervous System Tumors, pp 371–379, Wiley-Liss, New York, 1993
Einhorn LH, Burgess MA, Vallejos C, Bodey GP, Gutterman J, Mavligit G, Hersh EM, Luce JK, Frei E, Freireich EJ, Gottlieb JA: Prognostic correlations and response to treatment in advanced metastatic malignant melanoma. Cancer Res 34: 1995–2004, 1974
Patel JK, Didolkar MS, Pickren JW, Moore RH: Metastatic pattern of malignant melanoma. A study of 216 autopsy cases. Am J Surg 135: 807–810, 1987
de la Monte SM, Moore GW, Hutchin M: Patterned distribution of metastases from malignant melanoma in humans. Cancer Res 43: 3427–3432, 1983
Chason JL, Walker FB, Landers JW: Metastatic carcinoma of the central nervous system and dorsal root ganglia: a prospective autopsy study. Cancer 16: 781–787, 1963
Amer MH, Al-Sarraf M, Baker LH, Vaitkevicius VK: Malignant melanoma and central nervous system metastases: incidence, diagnosis, treatment and survival. Cancer 42: 660–668, 1978
Byrne TN, Cascino TL, Posner JB: Brain metastasis from melanoma. J Neuro-Oncol 1: 313–317, 1981
Brunson KE, Beattie G, Nicolson GL: Selection and altered properties of brain-colonizing melanoma. Nature 272: 543–545, 1978
Miner KM, Kawaguchi T, Uba GW, Nicolson GL: Clonal drift of cell surface, melanogenic, and experimental metastatic properties ofin vivo-selected, brain-meninges-colonizing murine B16 melanoma. Cancer Res 42: 4631–4638, 1982
Kawaguchi T, Kawaguchi M, Dulski K, Nicolson GL: Cellular behavior of metastatic B16 melanoma in experimental blood-borne implantation and cerebral invasion. Invasion Metastasis 5: 16–30, 1985
Kawaguchi T, Kawaguchi M, Lembo T, Nicolson GL: Differential tumor growth of blood-borne B16 melanoma variants in cerebral dura mater is related to tumor-host reactions. Clin Exp Metastasis 7: 1–14, 1989
Schackert G, Fidler IJ: Site-specific metastasis of mouse melanomas and a fibrosarcoma in the brain or meninges of syngeneic animals. Cancer Res 48: 3478–3484, 1988
Schackert G, Price JE, Zhaang R, Bucana CD, Itoh K, Fidler IJ: Regional growth of different human melanomas as metastases in the brain of nude mice. Am J Pathol 136: 95–102, 1990
Ishikawa M, Fernandez B, Kerbel RS: Highly pigmented human melanoma variant which metastasizes widely in nude mice, including to skin and brain. Cancer Res 48: 4897–4903, 1988
Nicolson GL, Kawaguchi T, Kawaguchi M, Van Pelt C: Brain surface invasion and metastasis of murine malignant melanoma variants. J Neuro-Oncology 4: 209–218, 1987
Marchetti D, Menter D, Jin L, Nakajima M, Nicolson GL: Nerve growth factor effects on human and mouse melanoma cell invasion and heparanase production. Int J Cancer 55: 693–699, 1993
Belloni PN, Carney DH, Nicolson GL: Organ-derived endothelial cells exhibit differential responsiveness to thrombin and other growth factors. Microvasc Res 43: 20–45, 1992
Nakajima M, Irimura T, DiFerrante DT, DiFerrante N, Nicolson GL: Heparan sulfate degradation correlates with tumor invasive and metastatic properties of B16 melanoma sublines. Science 220: 611–613, 1983
Nakajima M, Irimura T, Di Ferrante N, Nicolson GL: Metastatic melanoma cell heparanase: characterization of heparan sulfate degradation fragments produced by B16 melanoma endoglucuronidase. J Biol Chem 259: 2283–2290, 1984
Barrett AJ, Kirschke H: Cathepsin B, cathepsin H, cathepsin L. Meth Enzyol 80: 535–561, 1981
Barrett AJ: Cathepsin D: purification of isoenzymes from human and chicken liver. Biochem J 117: 601–607, 1970
Nakajima M, Welch DR, Belloni PN, Nicolson GL: Degradation of basement membrane type IV collagen and lung subendothelial matrix by rat mammary adenocarcinoma cell clones of differing metastatic potentials. Cancer Res 47: 4869–4876, 1987
Albini A, Iwamoto Y, Kleinmann HK, Martin GR, Aaronson SA, Kozlowski JM, McEwan RN: A rapidin vitro assay for quantitating the invasive potential of tumor cells. Cancer Res 47: 3239–3245, 1987
Herrmann JL, Menter DG, Hamada J-I, Marchetti D, Nakajima M, Nicolson GL: Mediation of NGF-stimulated extracellular matrix invasion by the human melanoma low-affinity p75 neurotrophin receptor: Melanoma p75 functions independent oftrkA. Mol Biol Cell 4: 1205–216, 1993
Inoue T, Cavanaugh PG, Nicolson GL: Differences in transferrin response and numbers of transferrin receptors in rat and human mammary carcinoma lines of different metastatic potentials. J Cell Physiol 156: 212–217, 1993
Nicolson GL, Inoue T, Van Pelt CS, Cavanaugh PG: Differential expression of a Mr ∿ 90, 000 cell surface transferrin receptor-related glycoprotein on murine B16 metastatic melanoma sublines selected for enhanced brain or ovary colonization. Cancer Res 50: 515–520, 1990
Cavanaugh PG, Nicolson GL: Purification and characterization of a Mr 66, 000 lung-derived paracrine growth factor that preferentially stimulates thein vitro proliferation of lung metastasizing tumor ceils. J Cell Biochem 43: 127–138, 1990
Nicolson GL: Metastatic tumor cell attachment and invasion assay utilizing vascular endothelial cell monolayers. J Histochem Cytochem 30: 214–220, 1982
Auerbach RL, Alby L, Morrissey W, Joseph J: Expression of organ specific antigens on capillary endothelial cells. Microvasc Res 29: 401–411, 1985
Belloni PN, Nicolson GL: Differential expression of cell surface glycoproteins on various organ-derived microvascular endothelia and endothelial cell cultures. J Cell Physiol 136: 398–410, 1988
Hempstead BL, Martin ZD, Kaplan DR, Parada LF, Chao MV: High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor. Nature 350: 678–683, 1991
Herlyn M, Kath R, Williams N, Valyi-Nagy I, Rodeck V: Growth regulatory factors for normal, premalignant and malignant human cells. Adv Cancer Res 54: 213–234, 1990
Nicolson GL: Cancer progression and growth: relationship of paracrine and autocrine growth mechanisms to organ preference of metastasis. Exp Cell Res 204: 171–180, 1993
Nicolson GL, Dulski KM: Organ specificity of metastatic tumor colonization is related to organ-selective growth properties of malignant cells. Int J Cancer 38: 289–294, 1986
Cavanaugh PG, Nicolson GL: Purification and some properties of a lung-derived growth factor that differentially stimulates the growth of tumor cell metastatic to the lung. Cancer Res 49: 3928–3933, 1989
Cavanaugh PG, Nicolson GL: Lung-derived growth factor that stimulates the growth of lung-metastasizing tumor cells: Identification as transferrin. J Cell Biochem 47: 261–271, 1991
Nicolson GL, Cavanaugh PG, Inoue T: Differential stimulation of the growth of lung-metastasizing tumor cells by lung (paracrine) growth factors: Identification of transferrin-like mitogens in lung tissue-conditioned medium. J Nat Cancer Inst Mgr 13: 153–161, 1992
Rodeck U, Becker D, Herlyn M: Basic fibroblast growth factor in human melanoma. Cancer Cells 3: 308–312, 1991
Nicolson GL: Tumor cell instability, diversification, and progression to the metastatic phenotype: From oncogene to oncofetal expression. Cancer Res 47: 1473–1487, 1987
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nicolson, G.L., Nakajima, M., Herrmann, J.L. et al. Malignant melanoma metastasis to brain: role of degradative enzymes and responses to paracrine growth factors. J Neuro-Oncol 18, 139–149 (1993). https://doi.org/10.1007/BF01050420
Issue Date:
DOI: https://doi.org/10.1007/BF01050420