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The murine CC chemokine, 6C-kine, inhibits tumor growth and angiogenesis in a human lung cancer SCID mouse model

dc.contributor.authorBurdick, Marie D.en_US
dc.contributor.authorStrieter, Robert M.en_US
dc.contributor.authorArenberg, Douglas A.en_US
dc.contributor.authorZlotnick, Alberten_US
dc.contributor.authorStrom, Scott R. B.en_US
dc.date.accessioned2006-09-08T19:57:16Z
dc.date.available2006-09-08T19:57:16Z
dc.date.issued2001-01en_US
dc.identifier.citationArenberg, Douglas A.; Zlotnick, Albert; Strom, Scott R. B.; Burdick, Marie D.; Strieter, Robert M.; (2001). "The murine CC chemokine, 6C-kine, inhibits tumor growth and angiogenesis in a human lung cancer SCID mouse model." Cancer Immunology, Immunotherapy 49(11): 587-592. <http://hdl.handle.net/2027.42/42085>en_US
dc.identifier.issn0340-7004en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/42085
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=11225989&dopt=citationen_US
dc.description.abstractThe recently described CC chemokine, 6C-kine, is unique in that it contains -six rather than the usual four conserved cysteines typical of this family. Furthermore, murine 6C-kine binds to one of the CXC chemokine receptors CXCR3, in addition to its other known receptor CCR7. We have shown that two other ligands of CXCR3, IP-10 and MIG, are potent inhibitors of tumor growth in severe combined immunodeficiency (SCID) mice. We postulated that murine 6C-kine may also inhibit tumor growth via inhibition of angiogenesis in this model. SCID mice ( n =6 per group) inoculated with A549 human lung cancer cells were treated with either 6C-kine (100 ng intra-tumor injection every other day) or control protein for 8 weeks. Tumors from murine 6C-kine-treated mice (288 ± 26 mm 3 ) were significantly smaller than tumors from control treated mice (788 ± 156 mm 3 , P =0.005). Additionally, murine 6C-kine reduced metastases compared with controls (0.5 ± 0.3 vs 3.0 ± 1.2 metastases per animal, P =0.05). Tumor vascularity (as assessed by vessel density counting) was reduced in murine 6C-kine-treated mice compared with controls. Murine 6C-kine had no direct effect on proliferation of A549 cells, and there were no differences in the infiltration of leukocyte sub-populations, assessed by flow cytometry, in the treatment groups. Interestingly, human 6C-kine, unlike murine 6C-kine, does not bind CXCR3 and had no anti-tumor effect in the same model. These data suggest that murine 6C-kine has anti-tumor effects independent of its leukocyte-recruiting activity. Furthermore, while not confirmatory, these data lend further support to the fact that CXCR3 may be the receptor for angiostatic CXC chemokines.en_US
dc.format.extent103120 bytes
dc.format.extent3115 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypetext/plain
dc.language.isoen_US
dc.publisherSpringer-Verlag; Springer-Verlag Berlin Heidelbergen_US
dc.subject.otherAnimal Modelsen_US
dc.subject.otherKey Words Cytokineen_US
dc.subject.otherTumoren_US
dc.subject.otherAngiogenesisen_US
dc.subject.otherLegacyen_US
dc.titleThe murine CC chemokine, 6C-kine, inhibits tumor growth and angiogenesis in a human lung cancer SCID mouse modelen_US
dc.typeArticleen_US
dc.subject.hlbsecondlevelMicrobiology and Immunologyen_US
dc.subject.hlbsecondlevelBiological Chemistryen_US
dc.subject.hlbtoplevelScienceen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumDepartment of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0642, USA, USen_US
dc.contributor.affiliationumDepartment of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0642, USA, USen_US
dc.contributor.affiliationotherDepartment of Medicine, Division of Pulmonary & Critical Care Medicine, University of California Los Angeles (UCLA), Los Angeles, CA 90095-1690, USA, USen_US
dc.contributor.affiliationotherDNAX Research Institute, Palo Alto, CA 94394-1104, USA, USen_US
dc.contributor.affiliationotherDepartment of Medicine, Division of Pulmonary & Critical Care Medicine, University of California Los Angeles (UCLA), Los Angeles, CA 90095-1690, USA, USen_US
dc.contributor.affiliationumcampusAnn Arboren_US
dc.identifier.pmid11225989en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/42085/1/262-49-11-587_10490587.pdfen_US
dc.identifier.doihttp://dx.doi.org/10.1007/s002620000147en_US
dc.identifier.sourceCancer Immunology, Immunotherapyen_US
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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