Animal Cancer Center, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.
BMC Vet Res. 2012 Nov 9;8:216. doi: 10.1186/1746-6148-8-216.
Chemokines play multiple roles in the development and progression in a variety of tumors. Chemokine (C-X-C motif) ligand 7 (CXCL7) has been found associated with pro-inflammatory responses, but its role in cancer growth remains unclear. Our previous study showed that R phase tumor infiltrating lymphocytes (TILs) produced large amounts of interleukin (IL)-6 which antagonized transforming growth factor (TGF)-β derived from CTVT to diminish the immune-suppressive microenvironment. Now we intend to determine the expression pattern of CXCL7 and the role of IL-6/TGF-β in CXCL7 induction during spontaneous progressive (P) and regressive (R) phases in canine transmissible venereal tumor (CTVT).
We have demonstrated that CXCL7 expressed at high level in P phase and down-regulated in R phase by western blot and real-time PCR. This suggested that CXCL7 expression was negatively correlated with the tumor growth. Co-culturing TILs with CTVT cells was found to reduce CXCL7 expression, while adding IL-6 blocking antibody reversed it. Moreover, in P phase CTVT, while IL-1β and TGF-β had no obvious effect on CXCL7 expression, IL-6 was found significantly to reduce CXCL7 expression in a dose-dependent manner. The mRNA expression results of CXCL7 receptor, CXCR2, further confirmed the effects of IL-6 concentration on the CXCL7 expression.
CXCL7 overexpression might be associated with the progressive growth of CTVT. The results shown here also suggest the role of CXCL7 in cancer development and the potential as the anti-cancer therapeutic target.
趋化因子在多种肿瘤的发生和发展中发挥多种作用。趋化因子（C-X-C 基序）配体 7（CXCL7）已被发现与促炎反应有关，但它在肿瘤生长中的作用尚不清楚。我们之前的研究表明，有丝分裂期肿瘤浸润淋巴细胞（TIL）产生大量白细胞介素（IL）-6，拮抗来自 CTVT 的转化生长因子（TGF）-β，从而减少免疫抑制微环境。现在，我们打算确定 CXCL7 的表达模式以及 IL-6/TGF-β 在犬传染性性病肿瘤（CTVT）自发进展（P）和消退（R）阶段诱导 CXCL7 中的作用。
我们通过 Western blot 和实时 PCR 证明，CXCL7 在 P 期高表达，在 R 期下调。这表明 CXCL7 的表达与肿瘤生长呈负相关。共培养 TIL 与 CTVT 细胞被发现降低 CXCL7 的表达，而添加 IL-6 阻断抗体则逆转了这一现象。此外，在 P 期 CTVT 中，虽然 IL-1β 和 TGF-β 对 CXCL7 表达没有明显影响，但发现 IL-6 以剂量依赖性方式显著降低 CXCL7 的表达。CXCL7 受体 CXCR2 的 mRNA 表达结果进一步证实了 IL-6 浓度对 CXCL7 表达的影响。
CXCL7 的过表达可能与 CTVT 的进行性生长有关。这里的结果还表明 CXCL7 在癌症发展中的作用及其作为抗癌治疗靶点的潜力。
