Somatostatin Derivate (smsDX) Attenuates the TAM-Stimulated Proliferation, Migration and Invasion of Prostate Cancer via NF-κB Regulation.
Somatostatin Derivate (smsDX) Attenuates the TAM-Stimulated Proliferation, Migration and Invasion of Prostate Cancer via NF-κB Regulation.
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DOI：
10.1371/journal.pone.0124292
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Guo Z;Xing Z;Cheng X;Fang Z;Jiang C;Su J;Zhou Z;Xu Z;Holmberg A;Nilsson S;Liu Z
肿瘤的发生和发展受周围微环境中巨噬细胞的影响。为了研究炎症性肿瘤微环境对前列腺癌生长和转移的影响，本研究使用前列腺癌（PCa）细胞与肿瘤相关巨噬细胞（TAM）条件培养基（MCM）的共培养模型。MCM促进PCa细胞（LNCaP、DU 145和PC-3）的生长，并且裸鼠移植瘤模型一致地证明MCM可促进肿瘤生长。MCM在体外也能促进细胞的迁移和侵袭。生长抑素衍生物（smsDX）可显著抑制TAM刺激的前列腺癌细胞增殖、迁移和侵袭。免疫组化结果显示NF-κB在前列腺癌和BPH慢性炎症组织中呈高表达，且与巨噬细胞浸润呈正相关。进一步的研究表明，NF-κB在巨噬细胞浸润中起重要作用。SmsDX抑制TAM和PCa细胞之间的旁分泌环路，可能是PCa的潜在治疗剂。
Tumor development and progression are influenced by macrophages of the surrounding microenvironment. To investigate the influences of an inflammatory tumor microenvironment on the growth and metastasis of prostate cancer, the present study used a co-culture model of prostate cancer (PCa) cells with tumor-associated macrophage (TAM)-conditioned medium (MCM). MCM promoted PCa cell (LNCaP, DU145 and PC-3) growth, and a xenograft model in nude mice consistently demonstrated that MCM could promote tumor growth. MCM also stimulated migration and invasion in vitro. Somatostatin derivate (smsDX) significantly attenuated the TAM-stimulated proliferation, migration and invasion of prostate cancer. Immunohistochemistry revealed that NF-κB was over-expressed in PCa and BPH with chronic inflammatory tissue specimens and was positively correlated with macrophage infiltration. Further investigation into the underlying mechanism revealed that NF-κB played an important role in macrophage infiltration. SmsDX inhibited the paracrine loop between TAM and PCa cells and may represent a potential therapeutic agent for PCa.
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