Interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis
Tóm tắt
The incidence of brain metastasis is increasing, however, little is known about molecular mechanism responsible for lung cancer-derived brain metastasis and their development in the brain. In the present study, brain pathology was examined in an experimental model system of brain metastasis as well as in human brain with lung cancer metastasis. In an experimental model, after 3–6 weeks of intracardiac inoculation of human lung cancer-derived (HARA-B) cells in nude mice, wide range of brain metastases were observed. The brain sections showed significant increase in glial fibrillary acidic protein (GFAP)-positive astrocytes around metastatic lesions. To elucidate the role of astrocytes in lung cancer proliferation, the interaction between primary cultured mouse astrocytes and HARA-B cells was analyzed in vitro. Co-cultures and insert-cultures demonstrated that astrocytes were activated by tumor cell-oriented factors; macrophage migration inhibitory factor (MIF), interleukin-8 (IL-8) and plasminogen activator inhibitor-1 (PAI-1). Activated astrocytes produced interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β), which in turn promoted tumor cell proliferation. Semi-quantitative immunocytochemistry showed that increased expression of receptors for IL-6 and its subunits gp130 on HARA-B cells. Receptors for TNF-α and IL-1β were also detected on HARA-B cells but down-regulated after co-culture with astrocytes. Insert-culture with astrocytes also stimulated the proliferation of other lung cancer-derived cell lines (PC-9, QG56, and EBC-1). These results suggest that tumor cells and astrocytes stimulate each other and these mutual relationships may be important to understand how lung cancer cells metastasize and develop in the brain.
Tài liệu tham khảo
Schouten LJ, Rutten J, Huveneers HA, Twijnstra A (2002) Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer 94:2698–2705
Fidler IJ, Yano S, Zhang RD et al (2002) The seed and soil hypothesis: vascularisation and brain metastases. Lancet Oncol 3:53–57
Aloisi F, Ria F, Adorini L (2000) Regulation of T-cell responses by CNS antigen-presenting cells: different roles for microglia and astrocytes. Immunol Today 21:141–147
Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357:539–554
Fitzgerald DP, Palmieri D, Hua E et al (2008) Reactive glia are recruited by highly proliferative brain metastases of breast cancer and promote tumor cell colonization. Clin Exp Metastasis 25(7):799–810
Miller RH, Ffrench-Constant C, Raff MC (1989) The macroglial cells of the rat optic nerve. Annu Rev Neurosci 12:517–534
Aloisi F, Care A, Borsellino G et al (1992) Production of hemolymphopoietic cytokines (IL-6, IL-8, colony-stimulating factors) by normal human astrocytes in response to IL-1 beta and tumor necrosis factor-alpha. J Immunol 149:2358–2366
Hertz L, McFarlin DE, Waksman BH (1990) Astrocytes: auxiliary cells for immune responses in the central nervous system? Immunol Today 11:265–268
Lee SC, Liu W, Dickson DW et al (1993) Cytokine production by human fetal microglia and astrocytes. Differential induction by lipopolysaccharide and IL-1 beta. J Immunol 150:2659–2667
Wang FW, Jia DY, Du ZH et al (2009) Roles of activated astrocytes in bone marrow stromal cell proliferation and differentiation. Neuroscience 160(2):319–329
Sierra A, Price JE, Garcia-Ramirez M et al (1997) Astrocyte-derived cytokines contribute to the metastatic brain specificity of breast cancer cells. Lab Invest 77:357–368
Iguchi H, Tanaka S, Ozawa Y et al (1996) An experimental model of bone metastasis by human lung cancer cells: the role of parathyroid hormone-related protein in bone metastasis. Cancer Res 56:4040–4043
Lyons S, Kettenmann K (1998) Oligodendrocytes and microglia are selectively vulnerable to combined hypoxia and hypoglycemia injury in vitro. J Cereb Blood Flow Metab 18:521–530
Zhang M, Olsson Y (1995) Reactions of astrocytes and microglial cells around hematogenous metastases of the human brain. Expression of endothelin-like immunoreactivity in reactive astrocytes and activation of microglial cells. J Neurol Sci 134:26–32
Giavazzi R, Garofalo A, Bani MR et al (1990) Interleukin 1-induced augmentation of experimental metastases from a human melanoma in nude mice. Cancer Res 50:4771–4775
Vidal-Vanaclocha F, Amezaga C, Asumendi A et al (1994) Interleukin-1 receptor blockade reduces the number and size of murine B16 melanoma hepatic metastases. Cancer Res 54:2667–2672
Vidal-Vanaclocha F, Alvarez A, Asumendi A (1996) Interleukin 1 (IL-1)-dependent melanoma hepatic metastasis in vivo; increased endothelial adherence by IL-1-induced mannose receptors and growth factor production in vitro. J Natl Cancer Inst 88:198–205
Marchetti D, Denkins Y, Reiland J et al (2003) Brain-metastatic melanoma: a neurotrophic perspective. Pathol Oncol Res 9(3):147–158
Denkins Y, Reiland J, Roy M et al (2004) Brain metastases in melanoma: roles of neurotrophins. Neuro Oncol 6(2):154–165
Yoshida S, Takahashi H (2009) Expression of extracellular matrix molecules in brain metastasis. J Surg Oncol 100(1):65–68
Iguchi H, Onuma E, Sato K et al (2001) Involvement of parathyroid hormone-related protein in experimental cachexia induced by a human lung cancer-derived cell line established from a bone metastasis specimen. Int J Cancer 94(1):24–27
Funk JL, Trout CR, Wei H et al (2001) Parathyroid hormone-related protein (PTHrP) induction in reactive astrocytes following brain injury: a possible mediator of CNS inflammation. Brain Res 915(2):195–209
Bauer M, Gräbsch C, Gminski R et al (2010) Cement-related particles interact with proinflammatory IL-8 chemokine from human primary oropharyngeal mucosa cells and human epithelial lung cancer cell line A549. Environ Toxicol. doi:10.1002/tox.20643
Yang S, Su J, Cao J et al (2009) Establishment of a novel Chinese human lung adenocarcinoma cell line CPA-Yang1 which produces highly bone metastases in immunodeficient mice. Zhongguo Fei Ai Za Zhi 12(7):753–759
Liu Z, Xu S, Xiao N et al (2010) Overexpression of IL-8 and MMP-9 confer high malignant phenotype in patients with non-small cell lung cancer. Zhongguo Fei Ai Za Zhi 13(8):795–802
Crohns M, Saarelainen S, Laine S et al (2010) Cytokines in bronchoalveolar lavage fluid and serum of lung cancer patients during radiotherapy—association of interleukin-8 and VEGF with survival. Cytokine 50(1):30–36
Khan N, Cromer CJ, Campa M, Patz EF Jr (2004) Clinical utility of serum amyloid A and macrophage migration inhibitory factor as serum biomarkers for the detection of nonsmall cell lung carcinoma. Cancer 101(2):379–384
McClelland M, Zhao L, Carskadon S, Arenberg D (2009) Expression of CD74, the receptor for macrophage migration inhibitory factor, in non-small cell lung cancer. Am J Pathol 174(2):638–646
Liu Q, Yang H, Zhang SF (2010) Expression and significance of MIF and CD147 in non-small cell lung cancer. Sichuan Da Xue Xue Bao Yi Xue Ban 41(1):85–90
Rendon BE, Roger T, Teneng I et al (2007) Regulation of human lung adenocarcinoma cell migration and invasion by macrophage migration inhibitory factor. J Biol Chem 282(41):29910–29918
Offersen BV, Pfeiffer P, Andreasen P, Overgaard J (2007) Urokinase plasminogen activator and plasminogen activator inhibitor type-1 in nonsmall-cell lung cancer: relation to prognosis and angiogenesis. Lung Cancer 56(1):43–50
Ramer R, Rohde A, Merkord J et al (2010) Decrease of plasminogen activator inhibitor-1 may contribute to the anti-invasive action of cannabidiol on human lung cancer cells. Pharm Res 27(10):2162–2174
Chorostowska-Wynimko J, Kedzior M, Struniawski R et al (2010) Cell phenotype determines PAI-1 antiproliferative effect—suppressed proliferation of the lung cancer but not prostate cancer cells. Pneumonol Alergol Pol 78(4):279–283
Di Bernardo MC, Matakidou A, Eisen T, Houlston RS (2009) GELCAPS Consortium. Plasminogen activator inhibitor variants PAI-1 A15T and PAI-2 S413C influence lung cancer prognosis. Lung Cancer 65(2):237–241
Shetty S, Shetty P, Idell S et al (2008) Regulation of plasminogen activator inhibitor-1 expression by tumor suppressor protein p53. J Biol Chem 283(28):19570–19580
van der Poll T, Coyle SM, Kumar A et al (1997) Down-regulation of surface receptors for TNF and IL-1 on circulating monocytes and granulocytes during human endotoxemia: effect of neutralization of endotoxin-induced TNF activity by infusion of a recombinant dimeric TNF receptor. J Immunol 158(3):1490–1497
Mihara M, Ohsugi Y, Kishimoto T (2009) Evidence for the role of Th17 cell inhibition in the prevention of autoimmune diseases by anti-interluekin-6 receptor antibody. Biofactors 35(1):47–51
He BP, Wang JJ, Zhang X et al (2006) Differential reactions of microglia to brain metastasis of lung cancer. Mol Med 12(7–8):161–170