Invasive breast carcinoma cells from patients exhibit MenaINV- and macrophage-dependent transendothelial migration.
Invasive breast carcinoma cells from patients exhibit MenaINV- and macrophage-dependent transendothelial migration.
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DOI：
10.1126/scisignal.2005329
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发表时间：
2014-11-25
影响因子：
7.3
通讯作者：
Oktay MH
中科院分区：
文献类型：
--
作者：
Pignatelli J;Goswami S;Jones JG;Rohan TE;Pieri E;Chen X;Adler E;Cox D;Maleki S;Bresnick A;Gertler FB;Condeelis JS;Oktay MH
转移是一个复杂的、多步骤的癌症进展过程，几乎没有治疗选择。一个关键事件是癌细胞侵入血管（内渗），癌细胞通过血管内渗扩散到远处器官。在患者肿瘤样本中，Mena [一种表皮生长因子（EGF）响应性细胞迁移蛋白]丰度增加的乳腺癌细胞与巨噬细胞一起存在于称为TMEM位点（转移的肿瘤微环境）的内渗部位。此外，这些内渗部位的密度与患者的转移风险相关。我们发现，乳腺癌细胞的内渗可以通过阻断癌细胞和巨噬细胞之间的信号传导来防止。我们通过细针穿刺（FNA）活检从患者中获得了各种亚型的浸润性乳腺导管癌细胞，并发现在体外跨内皮迁移试验中，迁移通过人内皮细胞层的细胞富含编码MenaINV（Mena的一种侵袭性亚型）的转录本。这种增强的跨内皮迁移需要巨噬细胞，并且发生在所有乳腺癌亚型中。使用小鼠巨噬细胞和人癌细胞的FNAs，我们确定了旁分泌和自分泌激活集落刺激因子-1受体（CSF-1 R）。信号的旁分泌或自分泌性质取决于乳腺癌细胞亚型。敲除MenaINV或添加阻断CSF-1 R功能的抗体可阻止跨内皮迁移。我们的研究结果表明，MenaINV和TMEM频率是相关的预后标志物，CSF-1和MenaINV可能是预防多种乳腺癌亚型转移的治疗靶点。
Metastasis is a complex, multistep process of cancer progression that has few treatment options. A critical event is the invasion of cancer cells into blood vessels (intravasation), through which cancer cells disseminate to distant organs. Breast cancer cells with increased abundance of Mena [an epidermal growth factor (EGF)–responsive cell migration protein] are present with macrophages at sites of intravasation, called TMEM sites (for tumor microenvironment of metastasis), in patient tumor samples. Furthermore, the density of these intravasation sites correlates with metastatic risk in patients. We found that intravasation of breast cancer cells may be prevented by blocking the signaling between cancer cells and macrophages. We obtained invasive breast ductal carcinoma cells of various subtypes by fine-needle aspiration (FNA) biopsies from patients and found that, in an in vitro transendothelial migration assay, cells that migrated through a layer of human endothelial cells were enriched for the transcript encoding MenaINV, an invasive isoform of Mena. This enhanced transendothelial migration required macrophages and occurred with all of the breast cancer subtypes. Using mouse macrophages and the human cancer cells from the FNAs, we identified paracrine and autocrine activation of colony-stimulating factor-1 receptor (CSF-1R). The paracrine or autocrine nature of the signal depended on the breast cancer cell subtype. Knocking down MenaINV or adding an antibody that blocks CSF-1R function prevented transendothelial migration. Our findings indicate that MenaINV and TMEM frequency are correlated prognostic markers and CSF-1 and MenaINV may be therapeutic targets to prevent metastasis of multiple breast cancer subtypes.
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影响因子：
4.4
作者：
KACINSKI, BM
通讯作者：
KACINSKI, BM
DOI：
10.1073/pnas.1006732107
发表时间：
2010-10-19
影响因子：
11.1
作者：
Liu, Huiping;Patel, Manishkumar R.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.
影响因子：
2.3
作者：
Gupta, PK;Baloch, ZW
通讯作者：
Baloch, ZW
影响因子：
8
作者：
通讯作者：
--
影响因子：
11.2
作者：
Patsialou A;Wyckoff J;Wang Y;Goswami S;Stanley ER;Condeelis JS
通讯作者：
Condeelis JS