Abstract
We report here that breast cancer cells from spontaneous tumors that arise in rat neu transgenic mice produce several chemokines capable of acting upon cells of the immune system. Moreover, mice bearing these spontaneous tumors possess splenic T cells as well as CD11c+, CD11b+ and CD19+ cells with an altered sensitivity to recombinant chemokines compared to naïve mice. A comparison between T-cell migration and the level of chemokines produced by the tumor cells revealed that the altered chemotactic activity was not a direct consequence of tumor-derived chemokines. These data suggest that a growing tumor may indirectly alter leukocyte chemotactic activity.
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Peng L, Shu S, Krauss JC: Monocyte chemoattractant protein inhibits the generation of tumor-reactive T cells. Cancer Res 57: 4849-4854, 1997
Mrowietz U, Schwenk U, Maune S, Bartels J, Kupper M, Fichter I, Schroder JM, Schadendorf D: The chemokine RANTES is secreted by human melanoma cells and is associated with enhanced tumour formation in nude mice. Br J Cancer 79: 1025-1031, 1999
Youngs SJ, Ali SA, Taub DD, Rees RC: Chemokines induce migrational responses in human breast carcinoma cell lines. Int J Cancer 71: 257-266, 1997
Kurt RA, Baher A, Wisner KP, Tackitt S, Urba WJ: Chemokine receptor desensitization in tumor-bearing mice. Cell Immunol 207: 81-88, 2001
Guy CT, Webster MA, Schaller M, Parsons TJ, Carl RD, Muller WJ: Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. Proc Nat Acad Sci (Wash) 89: 10578-10582, 1992
Kurt RA, Whitaker R, Baher A, Seung S, Urba WJ: Spontaneous mammary carcinomas fail to induce an immune response in syngeneic FVBN202 neu transgenic mice. Int J Cancer 87: 688-694, 2000
Morris AJ, Malbon CC: Physiological regulation of G proteinlinked signaling. Phys Rev 79: 1373-1429, 1999
Saeki H, Moore AM, Brown MJ, Hwang ST: Secondary lymphoid tissue chemokine (SLC) and CC chemokine receptor 7 (CCR7) participate in the emigration pathway of mature dendritic cells from the skin to regional lymph nodes. J Immunol 162: 2472-2475, 1999
Campbell JJ, Junliang P, Butcher EC: Developmental switches in chemokine responses during T cell maturation. J Immunol 163: 2353-2357, 1999
Gunn MD, Tangemann K, Tam C, Cyster JG, Rosen SD, Williams LT: A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naive T lymphocytes. Proc Natl Acad Sci USA 95: 258-263, 1998
Rutledge BJ, Rayburn H, Rosenberg R, North RJ, Gladue RP, Corless CL, Rollins BJ: High level monocyte chemoattractant protein-1 expression in transgenic mice increases their susceptibility to intracellular pathogens. J Immunol 155: 4838-4843, 1995
Lukacs NW, Kunkel SL, Strieter RM, Chensue SW: The role of chemokines in schistosoma mansoni granuloma formation. Parasit Today 10: 322-324, 1994
Dabbagh K, Xiao Y, Smith C, Stepick-Biek P, Kim SG, Lamm WJ, Liggitt DH, Lewis DB: Local blockade of allergic airway hyperreactivity and inflammation by the poxvirus-derived pan-CC-chemokine inhibitor vCCI. J Immunol 165: 3418-3422, 2000
Fife BT, Kennedy KJ, Paniagua MC, Lukacs NW, Kunkel SL, Luster AD, Karpus WJ: CXCL10 (IFN-gamma-inducible protein-10) control of encephalitogenic CD4+ T cell accumulation in the central nervous system during experimental autoimmune encephalomyelitis. J Immunol 166: 7617-7624, 2001
Neumark E, Anavi R, Witz IP, Ben-Baruch A: MCP-1 expression as a potent contributor to the high malignancy phenotype of murine mammary adenocarcinoma cells. Immunol Lett 68: 141-146, 1999
Bacon KB, Premack BA, Gardner P, Schall TJ: Activation of dual signaling pathways by the chemokine RANTES. Science 269: 1727-1730, 1995
Appay V, Dunbar PR, Cerundolo V, McMichael A, Czaplewski L, Rowland-Jones S: RANTES activates antigenspecific cytotoxic T lymphocytes in a mitogen-like manner through cell surface aggregation. Int Immunol 12: 1173-1182, 2000
Zou W, Machelon V, Coulomb-L'Herman A, Borvak J, Nome F, Isaeva T, Wei S, Krzysiek R, Durand-Gasselin I, Gordon A, Pustilnik T, Curiel DT, Galanaud P, Capron F, Emilie D, Curiel TJ: Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells. Nat Med 7: 1339-1346, 2001
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Kurt, R.A., Bauck, M., Harma, S. et al. Altered Chemokine Receptor Sensitivity in FVBN202 Rat neu Transgenic Mice. Breast Cancer Res Treat 77, 225–232 (2003). https://doi.org/10.1023/A:1021853202515
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DOI: https://doi.org/10.1023/A:1021853202515