Ayala Gustavo E, Dai Hong, Tahir Salahaldin A, Li Rile, Timme Terry, Ittmann Michael, Frolov Anna, Wheeler Thomas M, Rowley David, Thompson Timothy C
Departments of Pathology, Urology, and Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Cancer Res. 2006 May 15;66(10):5159-64. doi: 10.1158/0008-5472.CAN-05-1847.
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-beta1 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.
小窝蛋白-1（cav-1）是细胞膜内陷（小窝）的主要支架成分。它参与隔离众多效应器和信号分子，并在前列腺癌中具有抗凋亡活性。神经周围浸润（PNI）在人体组织和体外PNI模型中均与癌细胞凋亡减少有关。我们在此表明，cav-1的基质（神经束膜）产生参与了PNI中的旁分泌抗凋亡环路。随着癌细胞靠近神经，转化生长因子-β1在癌细胞中上调，并且被认为可上调前列腺癌神经神经束膜中的cav-1。然后，Cav-1被分泌到微环境中，并被前列腺癌细胞用来抑制凋亡。在体外PNI模型中，通过中和cav-1抗体或使用来自cav-1基因敲除小鼠的神经节，这种现象可部分逆转。我们的结果显示了PNI中的前列腺癌用于增加其增殖活性并减少凋亡的一种新的旁分泌机制。
