A Unidirectional Transition from Migratory to Perivascular Macrophage Is Required for Tumor Cell Intravasation.
A Unidirectional Transition from Migratory to Perivascular Macrophage Is Required for Tumor Cell Intravasation.
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DOI：
10.1016/j.celrep.2018.04.007
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发表时间：
2018-05-01
期刊：
影响因子：
8.8
通讯作者：
Condeelis JS
中科院分区：
文献类型：
--
作者：
Arwert EN;Harney AS;Entenberg D;Wang Y;Sahai E;Pollard JW;Condeelis JS
肿瘤相关巨噬细胞（TAM）是肿瘤转移的关键。两个TAM亚群支持癌细胞内渗：迁移性巨噬细胞引导癌细胞朝向血管，其中固着的血管周围巨噬细胞帮助它们进入血液。然而，很少有人知道这些功能不同的TAM之间的相互关系或它们可能的相互转换。我们发现，能动的，流动的TAM是新到达的单核细胞，通过CCR 2信号转导，然后分化成无柄的血管周围巨噬细胞。这个单向过程由CXCL 12和CXCR 4调节。癌细胞诱导单核细胞中CXCR 4的TGF-β依赖性上调，而血管周围成纤维细胞表达的CXCL 12将这些能动的TAM吸引到血管中，从而将能动的癌细胞带到血管中。一旦在血管上，迁移性TAM分化成血管周围巨噬细胞，促进血管渗漏和内渗。运动的TAM通过单向过程变成固着的血管周围TAM TAM通过CCR 2信号传导募集TAM，然后肿瘤来源的TGF-β诱导CXCR 4 CXCR 4阳性TAM向表达CXCL 12的血管周围癌症相关成纤维细胞（CAF）迁移。一旦在血管上，TAM变得固着并促进癌细胞内渗。Arwert等人显示，在外渗后，单核细胞最初变成能动的TAM。然后，肿瘤来源的TGF-β诱导TAM上的CXCR 4，刺激它们向表达CXCL 12的血管周围成纤维细胞迁移。一旦邻近血管，TAM分化为转移辅助血管周围TAM。
Tumor-associated macrophages (TAMs) are critical for tumor metastasis. Two TAM subsets support cancer cell intravasation: migratory macrophages guide cancer cells toward blood vessels, where sessile perivascular macrophages assist their entry into the blood. However, little is known about the inter-relationship between these functionally distinct TAMs or their possible inter-conversion. We show that motile, streaming TAMs are newly arrived monocytes, recruited via CCR2 signaling, that then differentiate into the sessile perivascular macrophages. This unidirectional process is regulated by CXCL12 and CXCR4. Cancer cells induce TGF-β-dependent upregulation of CXCR4 in monocytes, while CXCL12 expressed by perivascular fibroblasts attracts these motile TAMs toward the blood vessels, bringing motile cancer cells with them. Once on the blood vessel, the migratory TAMs differentiate into perivascular macrophages, promoting vascular leakiness and intravasation. Motile TAMs turn into sessile perivascular TAMs via a unidirectional process TAMs are recruited via CCR2 signaling, and then tumor-derived TGF-β induces CXCR4 CXCR4-positive TAMs migrate toward CXCL12-expressing perivascular cancer-associated fibroblasts (CAFs) Once on the blood vessel, TAMs become sessile and promote cancer cell intravasation Tumor-associated macrophages (TAMs) are essential for metastasis. Arwert et al. show that, following extravasation, monocytes initially become motile TAMs. Tumor-derived TGF-β then induces CXCR4 on TAMs, stimulating them to migrate toward CXCL12-expressing perivascular fibroblasts. Once adjacent to blood vessels, TAMs differentiate into metastasis-assisting perivascular TAMs.
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影响因子：
8
作者：
Leung E;Xue A;Wang Y;Rougerie P;Sharma VP;Eddy R;Cox D;Condeelis J
通讯作者：
Condeelis J
影响因子：
50.3
作者：
Lewis CE;Harney AS;Pollard JW
通讯作者：
Pollard JW
影响因子：
7.6
作者：
CHERAGHALI, AM;KNAUS, EE;WIEBE, LI
通讯作者：
WIEBE, LI
影响因子：
4.2
作者：
Clifford, A. B.;Elnaggar, A. M.;O'Neill, K.
通讯作者：
O'Neill, K.
影响因子：
7.3
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
通讯作者：
Oktay MH