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Nature:CCL2/白介素-6抑制剂的抗癌作用

标签:抗癌
摘要 : 炎性单核细胞以前被发现能够通过分泌如CCL2等细胞因子来渗透和促进转移瘤的生长。这曾导致以下发现:中和CCL2或阻断其受体CCR2也许会有治疗作用。然而,在一个乳腺癌小鼠模型中,Laura Bonapace 等人现在发现,与未治疗的病变相比,抗-CCL2疗法的中断不仅会使疗效停止,而且会加速肺转移瘤的生长和动物的死亡。

nature13862-sf2 

炎性单核细胞以前被发现能够通过分泌如CCL2等细胞因子来渗透和促进转移瘤的生长。这曾导致以下发现:中和CCL2或阻断其受体CCR2也许会有治疗作用。然而,在一个乳腺癌小鼠模型中,Laura Bonapace 等人现在发现,与未治疗的病变相比,抗-CCL2疗法的中断不仅会使疗效停止,而且会加速肺转移瘤的生长和动物的死亡。

这是由于骨髓单核细胞吸收量的猛增和肺转移瘤环境中依赖于白介素-6的血管化的增加。虽然这些发现说明对单独使用抗-CCL2药物需要谨慎,但作者也证明,将抗-CCL2疗法和抗白介素-6疗法相结合,在一个小鼠模型中能减少癌转移和提高存活率。

原文摘要:

Cessation of CCL2 inhibition accelerates breast cancer metastasis by promoting angiogenesis

Laura Bonapace, Marie-May Coissieux, Jeffrey Wyckoff, Kirsten D. Mertz, Zsuzsanna Varga, Tobias Junt & Mohamed Bentires-Alj

Secretion of C–C chemokine ligand 2 (CCL2) by mammary tumours recruits CCR2-expressing inflammatory monocytes to primary tumours and metastatic sites, and CCL2 neutralization in mice inhibits metastasis1 by retaining monocytes in the bone marrow. Here we report a paradoxical effect of CCL2 in four syngeneic mouse models of metastatic breast cancer. Surprisingly, interruption of CCL2 inhibition leads to an overshoot of metastases and accelerates death. This is the result of monocyte release from the bone marrow and enhancement of cancer cell mobilization from the primary tumour, as well as blood vessel formation and increased proliferation of metastatic cells in the lungs in an interleukin (IL)-6- and vascular endothelial growth factor (VEGF)-A-dependent manner. Notably, inhibition of CCL2 and IL-6 markedly reduced metastases and increased survival of the animals. CCL2 has been implicated in various neoplasias and adopted as a therapeutic target1, 2, 3. However, our results call for caution when considering anti-CCL2 agents as monotherapy in metastatic disease and highlight the tumour microenvironment as a critical determinant of successful anti-metastatic therapy.(doi: 10.1038/nature13862 & doi: 10.1038/nature13931

对应Nature杂志: 2014年11月06日Nature杂志精选

来源: Nature中文 浏览次数:237

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