密歇根州研究人員發(fā)現(xiàn)在腫瘤細胞扎根于骨髓之前使用普通化療藥物，實際上會讓腫瘤細胞更容易進入骨髓,、生長,。
該研究為某些癌癥轉移到骨的機制提供了寶貴的思路，并有可能最終導致新的轉移預防藥物的出現(xiàn),。
雖然能有效攻擊腫瘤細胞,，環(huán)磷酰胺和許多其他化療藥物一樣具有副作用，會抑制骨髓細胞,，影響免疫系統(tǒng),。如果我們更好地理解其中機制，我們可以制定更有效的療法,，以防止局部癌癥蔓延,，從而減少轉移到骨。
真正的好消息是研究者通過抑制另一個骨髓中細胞間溝通的蛋白質(zhì)——CCL2,，逆轉了腫瘤藥物——環(huán)磷酰胺的效果,。McCauley說：這項工作仍處于早期臨床前的水平。（生物谷：Bioon.com）
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.
