The brain is a unique microenvironment enclosed by the skull, lacking lymphatic drainage and maintaining i highly regulated vascular transport barrier. To metastasize to the brain malignant tumor cells must attach to microvessel endothelial cells, respond to brain-derived invasion factors, invade the blood-brain barrier and respond to survival and growth factors. Trophic factors are important in brain invasion because they can act to stimulate this process. In responsive malignant cells trophic factors such as neurotrophins can promote invasion by enhancing the production of basement membrane-degradative enzymes (such as type IV collagenase/gelatinase and heparanase) capable of locally destroying the basement membrane and the blood-brain barrier. We examined human melanoma cell lines that exhibit varying abilities to form brain metastases. These melanoma lines express low-affinity neurotrophin receptor p75NTR in relation to their brain-metastatic potentials but the variants do not express trkA, the gene encoding a high affinity nerve growth factor (NGF) tyrosine kinase receptor p140trkA. Melanoma cells metastatic to brain also respond to paracrine factors made by brain cells. We have found that a paracrine form of transferrin is important in brain metastasis, and brain-metastatic cells respond to low levels of transferrin and express high levels of transferrin receptors. Brain-metastatic tumor cells can also produce autocrine factors any inhibitors that influence their growth, invasion and survival in the brain. We found that brain-metastatic melanoma cells synthesize transcripts for the following autocrine growth factors: TGFβ, bFGF, TGFα and IL-1β. Synthesis of these factors may influence the production of neurotrophins by adjacent brain cells, such as oligodendrocytes and astrocytes. Increased amounts of NGF were found in tumor-adjacent tissues at the invasion front of human melanoma tumors in brain biopsies. Trophic factors, autocrine growth factors, paracrine growth factors and other factors may determine whether metastatic cells can successfully invade, colonize and grow in the central nervous system.
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Steck PA and Nicolson GL, 1993, Metastasis to the central nervous system, In: Levine A and Schmidek H, eds. Molecular Genetics of Nervous System Tumors, New York: Wiley and Sons, pp 371–9.
Wright DC and Delaney TF, 1989, Treatment of metastatic cancer to the brain, In: DeVita VT, Hellman S and Rosenburg SA, eds. Cancer: principals and practice of oncology, New York: J. B. Lippincott Co, pp 2245–61.
Herlyn M, Thurin J, Balaban G et al. 1985, Characteristics of cultured human melanocytes isolated from different stages of tumor progression, Cancer Res, 45, 5670–6.
Albino AP, Davis BM and Nanus DM, 1991, Induction of growth factor RNA expression in human malignant melanoma: markers of transformation, Cancer Res, 51, 4815–20.
Nicolson GL, 1993, Paracrine and autocrine growth mechanisms in tumor metastasis to specific sites with particular emphasis on brain and lung metastasis, Cancer Metastasis Rev, 12, 325–43.
Raff CM, 1992, Social controls on cell survival and cell death, Nature, 356, 397–400.
Nowell PC, 1976, The clonal evolution of tumor cells, Science, 194, 23–8.
Raff MC, Barres BA, Burne JF et al. 1993, Programmed cell death and the control of cell survival: lessons from the nervous system, Science, 262, 695–700.
Snider WD, 1994, Functions of the neurotrophins during nervous system development: what knockouts are teaching us, Cell, 77, 627–38.
Menter DG, Herrmann JL, Marchetti D and Nicolson GL, 1995, in press, Involvement of neurotrophins and growth factors in brain metastasis formation, Invasion Metastasis, in press.
Bradshaw RA, Blundell TL, Lapatto R, McDonald NQ and Murray RJ, 1993, Nerve growth factor revisited, Trends Biochem Sci, 18, 48–52.
Ip NY and Yancopoulos GD, 1992, Ciliary neurotrophic factor and its receptor complex, Prog Growth Factor Res, 4, 139–55.
Johnson D, Lanahan A, Buck CR et al, 1986, Expression and structure of the human NGF receptor, Cell, 47, 545–54.
Maher PA, 1988, Nerve growth factor induces protein-tyrosine phosphorylation, Proc Natl Acad Sci USA, 85, 6788–91.
Miyasaka T, Chao MV, Sherline P and Saltiel AR, 1990, Nerve growth factor stimulates a protein kinase in PC-12 cells that phosphorylates microtubule-associated protein-2, J Biol Chem, 265, 4730–5.
Ohmichi M, Decker SJ and Saltiel AR, 1992, Nerve growth factor stimulates the tyrosine phosphorylation of a 38-kDa protein that specifically associates with the src homology domain of phospholipase C-gamma 1, J Biol Chem, 267, 21601–6.
Chao MV, 1992, Neurotrophin receptors: a window into neuronal differentiation, Neuron, 9, 583–93.
Meakin SO and Shooter EM, 1992, The nerve growth factor family of receptors, Trends Neurosci, 15, 323–31.
Barbacid M, 1993, Nerve growth factor: a tale of two receptors, Oncogene, 8, 2033–42.
Saltiel AR and Decker SJ, 1994, Cellular mechanisms of signal transduction for neurotrophins, BioEssays, 16, 405–11.
Kalcheim C, Carmeli C and Rosenthal A, 1992, Neurotrophin 3 is a mitogen for cultured neural crest cells, Proc Natl Acad Sci USA, 89, 1661–5.
Birren SJ, Lo L and Anderson DJ, 1993, Sympathetic neuroblasts undergo a developmental switch in trophic dependence, Development, 119, 597–610.
DiCicco BE, Friedman WJ and Black IB, 1993, NT-3 stimulates sympathetic neuroblast proliferation by promoting precursor survival, Neuron, 11, 1101–11.
Schnell L, Schneider R, Kolbeck R, Barde YA and Schwab ME, 1994, Neurotrophin-3 enhances sprouting of corticospinal tract during development and after adult spinal cord lesion, Nature, 367, 170–3.
Ernfors P, Lee KF, Kucera J and Jaenisch R, 1994, Lack of neurotrophin-3 leads to deficiencies in the peripheral nervous system and loss of limb proprioceptive afferents, Cell, 77, 503–12.
Klein R, Silos SI, Smeyne RJ et al. 1994, Disruption of the neurotrophin-3 receptor gene trkC eliminates la muscle afferents and results in abnormal movements, Nature, 368, 249–51.
Klein R, Smeyne RJ, Wurst W et al. 1993, Targeted disruption of the trkB neurotrophin receptor gene results in nervous system lesions and neonatal death, Cell, 75, 113–22.
Ernfors P, Lee KF and Jaenisch R, 1994, Mice lacking brain-derived neurotrophic factor develop with sensory deficits, Nature, 368, 147–50.
Jones KR, Farinas I, Backus C and Reichardt LF, 1994, Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development, Cell, 76, 989–99.
Crowley C, Spencer SD, Nishimura MC et al. 1994, Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain cholinergic neurons, Cell, 76, 1001–11.
Smeyne RJ, Klein R, Schnapp A et al, 1994, Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene, Nature, 368, 246–9.
Buchman VL and Davies AM, 1993, Different neurotrophins are expressed and act in a developmental sequence to promote the survival of embryonic sensory neurons, Development, 118, 989–1001.
Peacocke M, Yaar M, Mansur CP, Chao MV and Gilchrest BA, 1988, Induction of nerve growth factor receptors in cultured human melanocytes, Proc Natl Acad Sci USA, 85, 5282–6.
Yaar M and Gilchrest BA, 1991, Human melanocyte growth and differentiation: a decade of new data. J Invest Dermatol, 97, 611–7.
Yaar M, Eller MS, DiBenedetto P et al. 1994, The trk family of receptors mediates nerve growth factor and neurotrophin-3 effects in melanocytes, 94, 1550–62.
Herrmann JL, Menter DG, Hamada J et al. 1993, Mediation of NGF-stimulated extracellular matrix invasion by the human melanoma low-affinity p75 neurotrophin receptor: melanoma p75 functions independently of trkA, Mol Biol Cell, 4, 1205–16.
Verdi JM, Birren SJ, Ibanez CF et al. 1994, p75LNGFR regulates Trk signal transduction and NGF-induced neuronal differentiation in MAH cells, Neuron, 12, 733–45.
Rabizadeh S, Oh J, Zhong LT et al. 1993, Induction of apoptosis by the low-affinity NGF receptor, Science, 261, 345–8.
Kannan Y, Usami K, Okada M, Shimizu S and Matsuda H, 1992, Nerve growth factor suppresses apoptosis of murine neutrophils, Biochem Biophvs Res Commun, 186, 1050–6.
Beutler B and van Huffel C, 1994, Unraveling function in the TNF ligand and receptor families, Science, 264, 667–8.
Smith CA, Farrah T and Goodwin RG, 1994, The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death, Cell, 76, 959–62.
Barrett GL and Bartlett PF, 1994, The p75 nerve growth factor receptor mediates survival or death depending on stage of sensory neuron development, Proc Natl Acad Sci USA, 91, 6501–5.
Lee KF, Li E, Huber LJ et al. 1992, Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system, Cell, 69, 737–49.
Lee KF, Buchman K, Landis S and Jaenisch R, 1994, Dependence on p75 for innervation of some sympathetic targets, Science, 263, 1447–9.
Hempstead BL, Martin ZD, Kaplan DR, Parada LF and Chao MV, 1991, High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor, Nature, 350, 678–83.
Hempstead BL, Schleifer LS and Chao MV, 1989, Expression of functional nerve growth factor receptors after gene transfer, Science, 243, 373–5.
Berg MM, Sternberg DW, Hempstead BL and Chao MV, 1991, The low-affinity p75 nerve growth factor (NGF) receptor mediates NGF-induced tyrosine phosphorylation, Proc Natl Acad Sci USA, 88, 7106–10
von Bartheld CS, Kinoshita Y, Prevette D et al. 1994, Positive and negative effects of neurotrophins on the isthmo-optic nucleus in chick embryos, Neuron, 12, 639–54.
Meakin SO and Shooter EM, 1991, Molecular investigations on the high-affinity nerve growth factor receptor, Neuron, 6, 153–63.
Weksamp G and Reichardt LF, 1991, Evidence that biological activity of NGF is mediated through a novel subclass of high affinity receptors, Neuron, 6, 649–63.
Barker PA and Shooter EM, 1994, Disruption of NGF binding to the low affinity neurotrophin receptor p75LNTR reduces NGF binding to TrkA on PC12 cells, Neuron, 13, 203–15.
Feinstein DL and Larhammar D, 1990, Identification of a conserved protein motif in a group of growth factor receptors, FEES Lett, 272, 7–11.
Knipper M, Beck A, Rylett J and Breer H, 1993, Neurotrophin induced CAMP and IP3 responses in PC 12 cells. Different pathways, Febs Lett, 324, 147–52.
Hempstead BL, Patil N, Thiel B and Chao MV, 1990, Deletion of cytoplasmic sequences of the nerve growth factor receptor leads to loss of high affinity ligand binding, J Biol Chem, 265, 9595–8.
Hantzopoulos PA, Chitra S, Glass DJ, Goldfarb MP and Yancopoulos GD, 1994, The low affinity NGF receptor, p75, can collaborate with each of the trks to potentiate functional responses to the neurotrophins, Neuron, 13, 187–201.
Volonte C and Greene LA, 1992, Nerve growth factor-activated protein kinase N. Characterization and rapid near homogeneity purification by nucleotide affinity-exchange chromatography, J Biol Chem, 267, 21663–70.
Volonte C, Ross AH and Greene LA, 1993, Association of a purine-analogue-sensitive protein kinase activity with p75 nerve growth factor receptors, Mol Biol Cell, 4, 71–8.
Volonte C and Greene LA, 1990, Induction of ornithine decarboxylase by nerve growth factor in PC12 cells: dissection by purine analogues, J Biol Chem, 265, 11050–5.
Ohmichi M, Decker SJ, Pang L and Saltiel AR, 1991, Phospholipase C-gamma 1 directly associates with the p70 trk oncogene product through its src homology domains, J Biol Chem, 266, 14858–61.
Ohmichi M, Decker SJ and Saltiel AR, 1992, Activation of phosphatidylinositol-3 kinase by nerve growth factor involves indirect coupling of the trk proto-oncogene with src homology 2 domains, Neuron, 9, 769–77.
Rozakis-Adcock M, McGlade J, Mbamalu G et al. 1992, Association of the Shc and Grb2/Sem5 SH2-containing proteins is implicated in activation of the Ras pathway by tyrosine kinases, Nature, 360, 689–92.
Obermeier A, Halfter H, Wiesmuller KH et al. 1993, Tyrosine 785 is a major determinant of Trk-substrate interaction, EMBO J, 12, 933–41.
Obermeier A, Lammers R, Wiesmuller KH et al. 1993, Identification of Trk binding sites for SHC and phosphatidylinositol 3′-kinase and formation of a multimeric signaling complex, J Biol Chem, 268, 22963–6.
Borrello MG, Pelicci G, Arighi E et al. 1994, The oncogenic versions of the Ret and Trk tyrosine kinases bind Shc and Grb2 adaptor proteins, Oncogene, 9, 1661–8.
Ohmichi M, Matuoka K, Takenawa T and Saltiel AR, 1994, Growth factors differentially stimulate the phosphorylation of Shc proteins and their association with Grb2 in PC-12 pheochromocytoma cells, J Biol Chem, 269, 1143–8.
Stephens RM, Loeb DM, Copeland TD et al. 1994, Trk receptors use redundant signal transduction pathways involving SHC and PLC-gamma 1 to mediate NGF responses, Neuron, 12, 691–705.
Obermeier A, Bradshaw RA, Seedorf K et al. 1994, Neuronal differentiation signals are controlled by nerve growth factor receptor/Trk binding sites for SHC and PLC gamma, EMBO J, 13, 1585–90.
Satoh T, Nakafuku M and Kaziro Y, 1992, Function of Ras as a molecular switch in signal transduction, J Biol Chem, 267, 24149–52.
Avruch J, Zhang X and Kyriakis JM, 1994, Raf meets Ras: completing the signal transduction pathway, Trends Biochem Sci, 19, 279–83.
Batistatou A, Volonte C and Greene LA, 1992, Nerve growth factor employs multiple pathways to induce primary response genes in PC12 cells, Mol Biol Cell, 3, 363–71.
Taylor LK, Swanson KD, Kerigan J, Mobley W and Landreth GE, 1994, Isolation and characterization of a nerve growth factor-regulated Fos kinase from PC 12 cells, J Biol Chem, 269, 308–18.
Lange-Carter CA and Johnson GL, 1994, Ras-dependent growth factor regulation of MEK kinase in PC12 cells, Science, 265, 1458–61.
Leevers SJ, Paterson HF and Marshall CJ, 1994, Requirement for Ras in Raf activation is overcome by targeting Raf to the plasma membrane, Nature, 369, 411–4.
Stokoe D, Macdonald SG, Cadwallader K, Symons M and Hancock JF, 1994, Activation of Raf as a result of recruitment to the plasma membrane, Science, 264, 1463–7.
Wartmann M and Davis RJ, 1994, The native structure of the activated Raf protein kinase is a membrane-bound multi-subunit complex, J Biol Chem, 269, 6695–701.
Volente C, Angelastro JM and Greene LA, 1993, Association of protein kinases ERK1 and ERK2 with p75 nerve growth factor receptors, J Biol Chem, 268, 21410–5.
Ohmichi M, Pang L, Decker SJ and Saltiel AR, 1992, Nerve growth factor stimulates the activities of the raf-1 and the mitogen-activated protein kinases via the trk protooncogene, J Biol Chem, 267, 14604–10.
Dobrowsky RT, Werner MH, Castellino AM, Chao MV and Hannun YA, 1994, Activation of the sphyngomyelin cycle through the low-affinity neurotrophin receptor, Science, 265, 1596–9.
Wolff RA, Dobrowsky RT, Bielawaska A, Obeid LM and Hannun YA, 1994, Role of ceramide-activated protein phosphatase in ceramide-mediated signal transduction, J Biol Chem, 269, 19605–9.
Ross AH, Grob P, Bothwell M et al. 1984, Characterization of nerve growth factor receptor in neural crest tumors using monoclonal antibodies, Proc Natl Acad Sci USA, 81, 6681–5.
Morse HG, Gonzalez R, Moore GE and Robinson WA, 1992, Preferential chromosome 11q and/or 17q aberrations in short-term cultures of metastatic melanoma resections from the brain, Cancer Genet Cytogenet, 64, 118–26.
Ishikawa M, Dennis JW, Man S and Kerbel RS, 1988, Isolation and characterization of spontaneous wheat germ agglutinin-resistant human melanoma mutants displaying remarkably different metastatic profiles in nude mice, Cancer Res, 48, 665–70.
Marchetti D, Menter D, Jin L, Nakajima M and Nicolson GL, 1993, Nerve growth factor effects on human and mouse melanoma cell invasion and heparanase production, Int J Cancer, 55, 692–9.
Kaplan DR, Hempstead BL, Martin ZD, Chao MV and Parada LF, 1991, The trk proto-oncogene product: a signal transducing receptor for nerve growth factor, Science, 252, 554–8.
Zupan AA, Osborne PA, Smith CE et al. 1989, Identification, purification and characterization of truncated forms of the human nerve growth factor receptor, J Biol Chem, 264, 11714–20.
Buxser S, Puma P and Johnson GL, 1985, Properties of the nerve growth factor receptor. Relationship between receptor structure and affinity, J Biol Chem, 260, 1917–26.
Cavanaugh PG and Nicolson GL, 1989, Purification and some properties of lung-derived growth factor that differentially stimulates the growth of tumor cells metastatic to the lung, Cancer Res, 89, 3928–33.
Cavanaugh PG and Nicolson GL, 1991, Lung-derived growth factor for lung-metastasizing tumor cells: identification as a transferrin, J Cell Biochem, 47, 261–7.
Nicolson GL, Menter DG, Herrmann JL et al, 1994, Tumor metastasis to brain: role of endothelial cells, neurotrophins and paracrine growth factors, Crit Rev Oncogenesis, in press.
Inoue T, Cavanaugh PG, Steck PA, Brunner N and Nicolson GL, 1993, Differences in transferrin response and numbers of transferrin receptors in rat and human mammary carcinoma lines of different metastatic potentials, J Cell Physiol, 156, 212–7.
Mescher AL and Muniam SI, 1988, Transferrin and the growth-promoting effect of nerves, Int Rev Cytol, 110, 1–26.
Jia LB, Cavanaugh PG and Nicolson GL, 1994, Paracrine growth factors for metastatic breast cancer cells: cloning of three new transferrin-like growth factor cDNAs that may be involved in the growth stimulation of breast cancer cells at secondary sites, Proc Am Assoc Cancer Res, 35, 44.
Nicolson GL, 1993, Cancer progression and growth: relationship of paracrine and autocrine growth mechanisms to organ preference of metastasis, Exp Cell Res, 204, 171–80.
Connor JR, Menzies SL, StMartin SM and Mufson EJ, 1990, Cellular distribution of transferrin, ferritin and iron in normal and aged human brains, J Neurosci Res, 27, 595–611.
Constam DB, Philipp JP, Malipiero UV et al. Differential expression of transforming growth factor-beta 1, -beta 2 and -beta 3 by glioblastoma cells, astrocytes and microglia, J Immunol, 148, 1404–10.
Morris CM, Candy JM, Bloxham CA and Edwardson JA, 1992, Immunocytochemical localisation of transferrin in the human brain, Acta Anat (Basel), 143, 14–8.
Oh YJ, Markelonis GJ and Oh TH, 1993, Effects of interleukin-1 beta and tumor necrosis factor-alpha on the expression of glial fibrillary acidic protein and transferrin in cultured astrocytes, Glia, 8, 77–86.
Orita T, Akimura T, Nishizaki T et al, 1990, Transferrin receptors in injured brain, Acta Neuropathol (Berlin), 79, 686–8.
Hunter KE, Sporn MB and Davies AM, 1993, Transforming growth factor-betas inhibit mitogen-stimulated proliferation of astrocytes, Glia, 7, 203–11.
Fressinaud C, Laeng P, Labourdette G, Durand J and Vallat JM, 1993, The proliferation of mature oligodendrocytes in vitro is stimulated by basic fibroblast growth factor and inhibited by oligodendrocyte-type 2 astrocyte precursors, Dev Biol, 158, 317–29.
Merrill JE, 1992, Tumor necrosis factor alpha, interleukin 1 and related cytokines in brain development: normal and pathological, Dev Neurosci, 14, 1–10.
Fischer HG, Nitzgen B, Germann T et al, 1993, Differentiation driven by granulocyte-macrophage colony-stimulating factor endows microglia with interferon-gamma-independent antigen presentation function, J Neuroimmunol, 42, 87–95.
Matsuda S, Fujita H, Imaoka S, Okumura N and Sakanaka M, 1993, Immunoelectron microscopic localization of basic FGF in neuroglias and neurons of the trigeminal mesencephalic and motor nuclei, Okajimas Folia Anat Jpn, 69, 335–43.
Alvarez JA, Baird A, Tatum A et al. 1992, Localization of basic fibroblast growth factor and vascular endothelial growth factor in human glial neoplasms, Mod Pathol, 5, 303–7.
Fabry Z, Fitzsimmons KM, Herlein JA et al. 1993, Production of the cytokines interleukin 1 and 6 by murine brain microvessel endothelium and smooth muscle pericytes, J Neuroimmunol, 47, 23–34.
Lindholm D, Hengerer B, Zafra F and Theonen H 1990, Transforming growth factor-beta 1 stimulates expression of nerve growth factor in the rat CNS, Neuroreport, 1, 9–12.
Lindholm D, Castren E, Kiefer R, Zafra F and Thoenen H, 1992, Transforming growth factor-beta 1 in the rat brain: increase after injury and inhibition of astrocyte proliferation, J Cell Biol, 117, 395–400.
Takamitsu F, Fan D, Staroselsky AH et al. 1993, Critical factors regulating site-specific brain metastasis of murine melanomas, Int J Oncol, 3, 789–99.
Ono T, Saito H, Kishimoto T, Okumoto T and Miyamoto K, 1991, Stimulation of biosynthesis of nerve growth factor by acidic fibroblast growth factor in cultured mouse astrocytes, Neurosci Lett, 126, 18–20.
Yoshida K and Gage FH, 1991, Fibroblast growth factors stimulate nerve growth factor synthesis and secretion by astrocytes, Brain Res, 538, 118–26.
Yoshida K and Gage FH, 1992, Cooperative regulation of nerve growth factor synthesis and secretion in fibroblasts and astrocytes by fibroblast growth factor and other cytokines. Brain Res, 569, 14–25.
Yoshida K, Kakihana M, Chen LS et al. 1992, Cytokine regulation of nerve growth factor-mediated cholinergic neurotrophic activity synthesized by astrocytes and fibroblasts, J Neurochem, 59, 919–31.
Yoshida T and Takeuchi M, 1993, Establishment of an astrocyte progenitor cell line: induction of glial fibrillary acidic protein and fibronectin by transforming growth factor-beta 1, J Neurosci Res, 35, 129–37.
Lu C, Vickers MF and Kerbel RS 1992, Interleukin 6: a fibroblast-derived growth inhibitor of human melanoma cells from early but not advanced stages of tumor progression, Proc Natl Acad Sci USA, 89, 9215–9.
Sawada M, Suzumura A and Marunouchi T, 1992, TNF alpha induces IL-6 production by astrocytes but not by microglia, Brain Res, 583, 296–9.
Zafra F, Lindholm D, Castren E, Hartikka J and Thoenen H, 1992, Regulation of brain-derived neurotrophic factor and nerve growth factor mRNA in primary cultures of hippocampal neurons and astrocytes, J Neurosci, 12, 4793–9.
Sendtner M, Arakawa Y, Stockli KA, Kreutzberg GW and Thoenen H, 1991, Effect of ciliary neurotrophic factor (CNTF) on motoneuron survival, J Cell Sci Suppl, 15, 103–9.
Menter DG, Herrmann JL and Nicolson GL, 1994, The metastatic melanoma neurotrophin receptor (p75) is a cell survival (menocytosis) receptor, Clin Exp Metastasis, 12, 82a.
Levi MR, 1987, The nerve growth factor 35 years later, Science, 237, 1154–62.
Norenberg MD, 1994, Astrocyte responses to CNS injury, J Neuropath Exp Neurol, 53, 213–20.
Wilken GP, Marriot DR and Chlolewinski AJ, 1990, Astrocyte heterogeneity, Trends Neurosci, 13, 43–6.
Kettenmann H, Orkand RK and Schachner M, 1983, Coupling among identified cells in mammalian nervous system cultures, J Neurosci, 3, 506–16.
Kimelberg HK and Ransom BR, 1986, Physiological aspects of astrocyte swelling, In: Fedoroff S and Verandakis A eds. Astrocytes, Orlando: Academic Press, pp 129–66.
Hirano A, Kawanami T and Llena JF, 1994, Electron microscopy of the blood brain barrier, Microsc Res Tech, 27, 543–56.
Lantos PL, Luthert PJ and Deane BR, 1984, Vascular permeability and cerebral oedema in experimental brain tumors. In: Inaba Y, Klatzo and Spatz M eds. Brain Edema, New York: Springer-Verlag, pp 40–7
Klatzo I, Chui E, Fujiwara K and Spatz M, 1980, Resolution of vasogenic brain edema (VBE), Adv Neurol, 28, 359–73.
Frank E, Pulver M and DeTribolet N, 1986, Expression of class II major histocompatibility antigens on reactive astrocytes and endothelial cells within gliosis surrounding metastases and abscesses, J Neuroimmunol, 12, 29–36.
Kristt DA, Reedy E and Yarden Y, 1993, Receptor tyrosine kinase expression in astrocytic lesions: similar features in gliosis and glioma, Neurosurg, 33, 106–15.
Strand FL, Zuccarelli LA, Williams KA et al, 1993, Melanotropins as growth factors, In: Vaudry H and Eberle AN eds. The melanotropic peptides, Ann N Y Acad Sci, 680, 29–50.
Mbikay M, Seidah and NG and Chretien M, 1993, From pro-opiomelanocortin to cancer, possible role of convertases in neoplasia, In: Vaudry H and Eberle AN eds. The melanotropic peptides, Ann N Y Acad Sci, 680, 13–9.
Jegou S, Blasquez C, Delbende C, Bunel DT and Vaudry H, 1993, Regulation of a-melanocyte-stimulating hormone release from hypothalamic neurons, In: Vaudry H and Eberle AN eds. The melanotropic peptides, Ann N Y Acad Sci, 680, 260-78.
Banks WA and Kastin AJ, 1992, Bidirectional passage of peptides across the blood brain barrier, Prog Brain Res, 91, 139–48.
Eberle AN, Siegrist W, Bagutti C et al. 1993, Receptors for melanocyte stimulating hormone on melanoma cells, In: Vaudry H and Eberle AN eds. The melanotropic peptides, Ann N Y Acad Sci, 680, 320-41.
Mountjoy KG, Robbins LS, Mortrund MT and Cone RD, 1992, The cloning of a family of genes that encode the melanocortin receptors, Science, 257, 1248–51.
Salomon Y, Zohar M, Dejordy JO et al. 1993, Signaling mechanisms controlled by melanocortins in melanoma, lacrimal and brain astroglial cells, In: Vaudry H and Eberle AN (eds.), The melanotropic peptides, Ann N Y Acad Sci, 680, 364-79.
Bennett DC, Holmes A, Devlin L and Hart IR, 1994, Experimental metastasis and differentiation of murine melanoma cells: actions and interactions of factors affecting different intracellular signaling pathways, Clin Exp Metastasis, 12, 385–97.
Siegrist W, Stutz S and Eberle AN, 1994, Homologous and heterologous regulation of a-melanocyte stimulating hormone receptors in human and mouse melanoma cell lines, Cancer Res, 54, 2604–10.
Kameyama K, Vieira WD, Tsukamoto K, Law LW and Hearing VJ, 1990, Differentiation and the tumorigenic and metastatic phenotype of murine melanoma cells, Int J Cancer, 45, 1151–8.
Hiltz ME, Catania A and Lipton JM, 1992, Alpha-MSH peptides inhibit acute inflammation induced in mice by rIL-1 beta, rIL-6, rTNF-alpha and endogenous pyrogen but not that caused by LTB-4, PAF and rIL-8, Cytokine, 4, 320–8.
Ceriani G, Macaluso A, Catania A and Lipton JM, 1994, Central neurogenic anti-inflammatory action of alpha-MSH: modulation of peripheral inflammation induced by cytokines and other mediators of inflammation, Neuroendocrinol, 59, 138–43.
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Menter, D.G., Herrmann, J.L. & Nicolson, G.L. The role of trophic factors and autocrine/paracrine growth factors in brain metastasis. Clin Exp Metast 13, 67–88 (1995). https://doi.org/10.1007/BF00133612
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DOI: https://doi.org/10.1007/BF00133612