Progression of prostate carcinoma is promoted by adipose stromal cell-secreted CXCL12 signaling in prostate epithelium.
Progression of prostate carcinoma is promoted by adipose stromal cell-secreted CXCL12 signaling in prostate epithelium.
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DOI：
10.1038/s41698-021-00160-9
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发表时间：
2021-03-22
影响因子：
7.9
通讯作者：
Kolonin MG
中科院分区：
文献类型：
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作者：
Su F;Daquinag AC;Ahn S;Saha A;Dai Y;Zhao Z;DiGiovanni J;Kolonin MG
癌症的侵袭性与脂肪基质细胞（ASC）的肿瘤募集有关，肥胖时脂肪基质细胞的募集会增加。 ASC 通过尚未完全了解的分子途径促进癌症。在这里，我们证明，在 HiMyc 小鼠（一种前列腺癌的自发遗传模型）中，肥胖会促进前列腺肿瘤中的上皮-间质转化 (EMT)，并在药理 ASC 耗尽时受到抑制。肿瘤中的 CXCL12 表达与 ASC 募集相关，并定位于表达血小板衍生生长因子受体 Pdgfra 和 Pdgfrb 的基质细胞。通过使用组织特异性敲除模型进一步研究了基质细胞分泌的这种趋化因子在癌症进展中的作用。 Pdgfr + 谱系中CXCL12基因的ASC缺失抑制了肿瘤生长和EMT，表明基质是CXCL12的关键来源。临床样本分析显示，肥胖者瘤周脂肪间质的 CXCL12 表达增加，肿瘤中 Pdgfr/CXCL12 表达的相关增加与前列腺癌患者的生存率降低有关。我们的研究将 ASC 确定为 CXCL12 驱动肿瘤侵袭性的来源，并概述了治疗癌症进展的方法。
Aggressiveness of carcinomas is linked with tumor recruitment of adipose stromal cells (ASC), which is increased in obesity. ASC promote cancer through molecular pathways not fully understood. Here, we demonstrate that epithelial–mesenchymal transition (EMT) in prostate tumors is promoted by obesity and suppressed upon pharmacological ASC depletion in HiMyc mice, a spontaneous genetic model of prostate cancer. CXCL12 expression in tumors was associated with ASC recruitment and localized to stromal cells expressing platelet-derived growth factor receptors Pdgfra and Pdgfrb. The role of this chemokine secreted by stromal cells in cancer progression was further investigated by using tissue-specific knockout models. ASC deletion of CXCL12 gene in the Pdgfr + lineages suppressed tumor growth and EMT, indicating stroma as the key source of CXCL12. Clinical sample analysis revealed that CXCL12 expression by peritumoral adipose stroma is increased in obesity, and that the correlating increase in Pdgfr/CXCL12 expression in the tumor is linked with decreased survival of patients with prostate carcinoma. Our study establishes ASC as the source of CXCL12 driving tumor aggressiveness and outlines an approach to treatment of carcinoma progression.
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影响因子：
1.5
作者：
Cuttler, Anne S.;LeClair, Renee J.;Stohn, J. Patrizia;Wang, Qiaozeng;Sorenson, Christine M.;Liaw, Lucy;Lindner, Volkhard
通讯作者：
Lindner, Volkhard
影响因子：
50.3
作者：
Hanahan, Douglas;Coussens, Lisa M.
通讯作者：
Coussens, Lisa M.
DOI：
10.1073/pnas.1320318110
发表时间：
2013-12-10
影响因子：
11.1
作者：
Feig, Christine;Jones, James O.;Fearon, Douglas T.
通讯作者：
Fearon, Douglas T.
影响因子：
12.4
作者：
Daquinag, Alexes C.;Tseng, Chieh;Kolonin, Mikhail G.
通讯作者：
Kolonin, Mikhail G.
影响因子：
64.8
作者：
通讯作者：
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