exMCAM-Fc, an S100A8/A9-mediated-metastasis blocker, efficiently reduced the number of circulating tumor cells that appeared in the blood flow
exMCAM-Fc, an S100A8/A9-mediated-metastasis blocker, efficiently reduced the number of circulating tumor cells that appeared in the blood flow
复制标题
exMCAM-Fc 是一种 S100A8/A9 介导的转移阻断剂，可有效减少血流中出现的循环肿瘤细胞的数量
DOI：
10.1007/s11033-020-05495-3
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发表时间：
2020
影响因子：
2.8
通讯作者：
Sakaguchi Masakiyo
中科院分区：
文献类型：
--
作者：
Tomonobu Nahoko;Kinoshita Rie;Sakaguchi Masakiyo
肿瘤转移是癌症患者治疗失败和癌症相关死亡的主要原因，因此对肿瘤转移的治疗调控是癌症治疗的重要课题。我们报道S100A8/A9是S100A8和S100A9的异源二聚体复合物，其受体在嗜肺性癌症的转移中起着至关重要的作用，即当肺癌肿块存在于离肺较远的区域时，S100A8/A9也会从肺中积极分泌，然后由于癌细胞在其细胞表面具有S100A8/A9受体，从而将远处的癌细胞吸引到肺中。有趣的是，新开发的诱捕物之一exMCAM-Fc是一种与S100A8/A9受体之一的黑色素瘤细胞粘附分子（melanoma cell adhesion molecule， MCAM）细胞外区域的Fc融合蛋白，它可以阻止S100A8/A9与MCAM的相互作用，通过对S100A8/A9介导的癌细胞事件施加多种抑制作用，包括增强移动性、侵袭性和对内皮细胞的附着，有效地抑制了肺癌的转移。然而，尚不清楚诱饵是否会减少循环肿瘤细胞（CTCs）的数量，而循环肿瘤细胞在嗜器官癌转移的背景下被定义为实体细胞。在这里，我们首先证明了exMCAM-Fc有效地减少了黑色素瘤小鼠血流中的ctc数量。这一新发现强化了exMCAM-Fc对肿瘤转移的抑制作用。因此，我们预计exMCAM-Fc可能通过有效阻断危及生命的癌症转移而大大减少治疗失败。
Metastasis is the major cause of treatment failure in cancer patients and of cancer-associated death so that therapeutic regulation of metastasis is very important subject for the cancer treatment. We have been reported that S100A8/A9, a heterodimer complex of S100A8 and S100A9, and its receptors play a crucial role in the lung tropic cancer metastasis, i.e., S100A8/A9 is actively secreted from the lung when cancer mass exists even at remote area from the lung and then functions to attract the distant cancer cells to the lung since cancer cells own the S100A8/A9 receptor(s) on their cell surface. Interestingly, one of the newly developed decoys, exMCAM-Fc, a Fc fusion protein with the extracellular region of melanoma cell adhesion molecule (MCAM), one of the S100A8/A9 receptors, that could prevent the interaction of S100A8/A9 with MCAM, efficiently suppressed the lung tropic cancer metastasis through exerting the several inhibitory effects on the S100A8/A9-mediated cancer cell events including enhanced mobility, invasion and attachment to the endothelial cells. However, it still remains to clarify if the decoy will reduce the number of circulating tumor cells (CTCs) that are defined as substantial cells in the context of organ tropic cancer metastasis. Here, we first show that exMCAM-Fc effectively reduces the number of CTCs in the blood flow of the melanoma bearing mice. The novel finding reinforces the suppressive role of exMCAM-Fc on the cancer metastasis. We therefore expect that exMCAM-Fc may greatly contribute to reduce treatment failure by the efficient blocking of the life threatening cancer metastasis.