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

Citation
Da. Arenberg et al., The murine CC chemokine, 6C-kine, inhibits tumor growth and angiogenesis in a human lung cancer SCID mouse model, CANCER IMMU, 49(11), 2001, pp. 587-592
Citations number
25
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
CANCER IMMUNOLOGY IMMUNOTHERAPY
ISSN journal
03407004 → ACNP
Volume
49
Issue
11
Year of publication
2001
Pages
587 - 592
Database
ISI
SICI code
0340-7004(200101)49:11<587:TMCC6I>2.0.ZU;2-8
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 C XCR3, 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 growt h in severe combined immunodeficiency (SCID) mice. We postulated that murin e 6C-kine may also inhibit tumor growth via inhibition of angiogenesis in t his model. SCID mice (n = 6 per group) inoculated with A549 human lung canc er cells were treated with either 6C-kine (100 ng intra-tumor injection eve ry other day) or control protein for 8 weeks. Tumors from murine 6C-kine-tr eated mice (288 +/- 26 mm(3)) were significantly smaller than tumors from c ontrol 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 cel ls, and there were no differences in the infiltration of leukocyte sub-popu lations, 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. Furth ermore, while not confirmatory, these data lend further support to the fact that CXCR3 may be the receptor for angiostatic CXC chemokines.