Stromal antiapoptotic paracrine loop in perineural invasion of prostatic carcinoma
Stromal antiapoptotic paracrine loop in perineural invasion of prostatic carcinoma
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DOI：
10.1158/0008-5472.can-05-1847
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发表时间：
2006-05-15
期刊：
影响因子：
11.2
通讯作者：
Thompson, TC
中科院分区：
文献类型：
--
作者：
Ayala, GE;Dai, H;Thompson, TC
Caveolin-1（cav-1）是细胞膜内陷（caveolae）的主要支架成分。它参与螯合许多效应物和信号分子，并在前列腺癌中具有抗凋亡活性。神经周侵袭（PNI）与人体组织和体外PNI模型中癌细胞凋亡的减少有关。我们在这里表明，基质（神经束膜）生产的cav-1参与了旁分泌抗凋亡环PNI。当癌细胞接近神经时，转化生长因子-PI在癌细胞中上调，并且被认为上调前列腺癌神经束膜中的cav-1。Cav-1随后被分泌到微环境中，并被前列腺癌细胞用于抑制凋亡。在体外PNI模型中，通过中和cav-1抗体或使用来自cav-1敲除小鼠的神经节，这种现象被部分逆转。我们的研究结果显示了一种新的旁分泌机制，在PNI的前列腺癌，以增加其增殖活性和减少凋亡。
Caveolin-1 (cav-1) is a major scaffolding component of cell membrane invaginations (caveolae). It is involved in sequestering numerous effectors and signaling molecules and has antiapototic activities in prostate cancer. Perineural invasion (PNI) is associated with decreased apoptosis of cancer cells both in human tissues and the in vitro PNI model. We show here that stromal (perineurium) production of cav-1 is involved in a paracrine antiapoptotic loop in PNI. Transforming growth factor-PI is up-regulated in the cancer cells as they approach the nerve and is thought to up-regulate cav-1 in the perineurium of nerves with prostate cancer. Cav-1 is then secreted into the microenvironment and used by prostate cancer cells to inhibit apoptosis. In the in vitro PNI model, this phenomenon is partially reversed by neutralizing cav-1 antibodies or using ganglia from cav-1 knockout mice. Our results show a novel paracrine mechanism used by the prostate cancer in PNI to increase their proliferative activity and decrease apoptosis.