Cancer Res：CCL2是肿瘤骨转移的关键机制

密歇根州研究人员发现在肿瘤细胞扎根于骨髓之前使用普通化疗药物，实际上会让肿瘤细胞更容易进入骨髓、生长。

该研究为某些癌症转移到骨的机制提供了宝贵的思路，并有可能最终导致新的转移预防药物的出现。

虽然能有效攻击肿瘤细胞，环磷酰胺和许多其他化疗药物一样具有副作用，会抑制骨髓细胞，影响免疫系统。如果我们更好地理解其中机制，我们可以制定更有效的疗法，以防止局部癌症蔓延，从而减少转移到骨。

真正的好消息是研究者通过抑制另一个骨髓中细胞间沟通的蛋白质——CCL2，逆转了肿瘤药物——环磷酰胺的效果。McCauley说：这项工作仍处于早期临床前的水平。

doi:10.1158/0008-5472.CAN-11-2928
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Cyclophosphamide Creates a Receptive Microenvironment for Prostate Cancer Skeletal Metastasis

Serk In Park, Jinhui Liao, Janice E. Berry, Xin Li, Amy J. Koh, et al.

A number of cancers predominantly metastasize to bone, due to its complex microenvironment and multiple types of constitutive cells. Prostate cancer especially has been shown to localize preferentially to bones with higher marrow cellularity. Using an experimental prostate cancer metastasis model, we investigated the effects of cyclophosphamide, a bone marrow–suppressive chemotherapeutic drug, on the development and growth of metastatic tumors in bone. Priming the murine host with cyclophosphamide before intracardiac tumor cell inoculation was found to significantly promote tumor localization and subsequent growth in bone. Shortly after cyclophosphamide treatment, there was an abrupt expansion of myeloid lineage cells in the bone marrow and the peripheral blood, associated with increases in cytokines with myelogenic potential such as C-C chemokine ligand (CCL)2, interleukin (IL)-6, and VEGF-A. More importantly, neutralizing host-derived murine CCL2, but not IL-6, in the premetastatic murine host significantly reduced the prometastatic effects of cyclophosphamide. Together, our findings suggest that bone marrow perturbation by cytotoxic chemotherapy can contribute to bone metastasis via a transient increase in bone marrow myeloid cells and myelogenic cytokines. These changes can be reversed by inhibition of CCL2.