Knudsen Beatrice S, Miranti Cindy K
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
J Cell Biochem. 2006 Oct 1;99(2):345-61. doi: 10.1002/jcb.20934.
In the normal prostate epithelium, androgen receptor (AR) negative basal epithelial cells adhere to the substratum, while AR expressing secretory cells lose substratum adhesion. In contrast, prostate cancer cells both express AR and adhere to a tumor basement membrane. In this review, we describe the differential expression of integrins, growth factor receptors (GFRs), and AR in normal and cancerous epithelium. In addition, we discuss how signals from integrins, GFRs, and AR are integrated to regulate the proliferation and survival of normal and malignant prostate epithelial cells. While cell adhesion is likely of great importance when considering therapeutic approaches for treatment of metastatic prostate cancer, no data on integrin expression are available from tissues of prostate cancer metastasis. However, several drug targets that are upregulated after androgen ablative therapy regulate cell adhesion and thus novel targeted therapies indirectly interfere with cell adhesion mechanisms in prostate cancer cells.
在正常前列腺上皮中,雄激素受体(AR)阴性的基底上皮细胞附着于基底膜,而表达AR的分泌细胞则失去基底膜附着。相比之下,前列腺癌细胞既表达AR又附着于肿瘤基底膜。在本综述中,我们描述了整合素、生长因子受体(GFRs)和AR在正常和癌性上皮中的差异表达。此外,我们还讨论了整合素、GFRs和AR发出的信号如何整合以调节正常和恶性前列腺上皮细胞的增殖和存活。虽然在考虑转移性前列腺癌的治疗方法时,细胞黏附可能非常重要,但目前尚无前列腺癌转移组织中整合素表达的数据。然而,雄激素剥夺治疗后上调的几个药物靶点可调节细胞黏附,因此新型靶向治疗间接干扰前列腺癌细胞中的细胞黏附机制。