期刊
CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 49, 期 11, 页码 587-592出版社
SPRINGER-VERLAG
DOI: 10.1007/s002620000147
关键词
cytokine; angiogenesis; animal models; tumor
资金
- NATIONAL CANCER INSTITUTE [K08CA072543] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P50HL046487, P50HL060289] Funding Source: NIH RePORTER
- NCI NIH HHS [CA72543] Funding Source: Medline
- NHLBI NIH HHS [P50HL60289, P50HL46487] Funding Source: Medline
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 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.
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