IJC：黑色素瘤转移至大脑的分子机制

癌细胞从肿瘤部位扩散转移到身体其他组织器官对癌症病人来说是一种严重的威胁。据美国国家癌症研究所，大多数癌症新增病例都是癌症转移复发导致的，而不是新的癌症患者。几乎所有类型的癌症都会扩散到身体其他部位包括大脑在内。一旦转移性黑色素瘤细胞在大脑中根深蒂固，癌症病人通常只有几个月的生存期。<!--more-->

特拉维夫大学细胞研究和免疫学系Isaac Witz教授和他的团队一直钻研是什么导致转移性黑色素瘤细胞转移至大脑中的，以及转移性黑色素瘤细胞是如何在大脑环境中生存并增殖的。他们的研究实验发现，黑色素瘤细胞产生存在于脑组织中的两种趋化因子的受体，趋化因子由细胞分泌的小分子蛋白家族。这些受体可以诱发癌细胞定位于大脑组织中。

Witz教授说：存在于大脑和黑色素瘤细胞之间的趋化因子盒趋化因子受体的相互作用可能是潜在的治疗黑色素瘤方法。相关研究发表在<em>International Journal of Cancer</em>杂志上。

虽然转移是一个逐渐被理解的过程，但研究人员仍在试图揭开为什么癌症细胞会迁移。了解是什么让癌症细胞分化、传播以及到达新的组织器官的增殖也是至关重要的。

为了更好地理解黑色素瘤细胞转移至大脑中，研究人员在实验室中培养脑组织，然后分析脑组织细胞中表达的所有物质料。他们发现组织中的某些趋化因子，脑转移性黑色素瘤细胞表达相应的趋化因子受体，诱导癌细胞转移至大脑中。如果大脑释放一定的趋化因子，黑色素瘤细胞上的受体感受到这些趋化因子就会被“吸引”至大脑组织中。

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<img src="http://www.bioon.com/biology/UploadFiles/201209/2012092012234673.gif" alt="" width="115" height="150" border="0" />

<a title="" href="http://dx.doi.org/10.1002/ijc.27552" target="_blank">doi:10.1002/ijc.27552</a>
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<br/><strong>The metastatic microenvironment: Brain-derived soluble factors alter the malignant phenotype of cutaneous and brain-metastasizing melanoma cells.</strong><br/>


Anat Klein, Orit Sagi-Assif, Sivan Izraely, Tsipi Meshel, Metsada Pasmanik-Chor, Clara Nahmias, Pierre-Olivier Couraud, Neta Erez, Dave S.B. Hoon, Isaac P. Witz.

The working hypothesis of this study is that the interactions between the brain microenvironment and melanoma cells determine metastasis formation at this organ site. The aim of the study was to evaluate the contribution of such interactions to the formation of brain metastasis in nude mice xenografted with human melanoma cells. An insight into these interactions is an essential prerequisite for the development of effective targeted therapy for melanoma brain metastasis. We assessed the effects of soluble factors present in supernatants of short-term cultures of normal mouse brain (referred here after as brain-derived soluble factors) on several characteristics linked to melanoma brain metastasis. It was found that brain-derived soluble factors affect differentially cutaneous and brain-metastasizing melanoma cells variants in vitro. Such factors enhanced the viability of cutaneous melanoma cells but caused an S phase arrest followed by apoptosis of brain-metastasizing cells. Brain-derived soluble factors enhanced migration of melanoma cells metastasizing to the brain, but did not affect the migration of the cutaneous variants. Such factors upregulated the expression of the chemokine receptor CCR4 in both cutaneous and brain-metastasizing melanoma cells. It is not unlikely that CCR4 ligands expressed in the brain interact with the CCR4-expressing melanoma cells thereby directing them to the brain. Brain-derived soluble factors enhanced the transmigration, across human brain endothelial cells of cutaneous but not of brain-metastasizing melanoma variants. This activity could promote the capacity of the cutaneous cells to metastasize to the brain.

<br/>来源：生物谷

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