The murine CC chemokine, 6C-kine, inhibits tumor growth and angiogenesis in a human lung cancer SCID mouse model (original) (raw)
Abstract
The 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 mm3) were significantly smaller than tumors from control treated mice (788 ± 156 mm3, _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.
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Authors and Affiliations
- Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0642, USA, , , , , , US
Douglas A. Arenberg & Scott R. B. Strom - DNAX Research Institute, Palo Alto, CA 94394-1104, USA, , , , , , US
Albert Zlotnick - Department of Medicine, Division of Pulmonary & Critical Care Medicine, University of California Los Angeles (UCLA), Los Angeles, CA 90095-1690, USA, , , , , , US
Marie D. Burdick & Robert M. Strieter
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- Douglas A. Arenberg
You can also search for this author inPubMed Google Scholar - Albert Zlotnick
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Received: 15 June 2000 / Accepted: 18 August 2000
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Arenberg, D., Zlotnick, A., Strom, S. et al. The murine CC chemokine, 6C-kine, inhibits tumor growth and angiogenesis in a human lung cancer SCID mouse model.Cancer Immunol Immunother 49, 587–592 (2001). https://doi.org/10.1007/s002620000147
- Issue Date: January 2001
- DOI: https://doi.org/10.1007/s002620000147