Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, Alabama.
Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, Alabama.
Am J Pathol. 2012 Mar;180(3):1170-1178. doi: 10.1016/j.ajpath.2011.11.020. Epub 2012 Jan 6.
For men in the United States, prostate cancer (PCa) is the most frequent malignancy and the second leading cause of cancer mortality. The metastatic spread of PCa is responsible for most deaths related to PCa. Although KISS1 functions as a metastasis suppressor in various cancers, its expression levels and functions in PCa development and progression remain undetermined. The goals of this study were to correlate the expression levels of KISS1 in PCas with clinicopathologic characteristics and to assess the biological relevance of KISS1 to the viability and motility of PCa cells. Strong KISS1 staining was detected in benign prostate tissues, but the staining was weaker in primary and metastatic PCas (both P < 0.001, t-test). Furthermore, the low expression levels of KISS1 in PCas correlated with clinical stage (P < 0.01) and with KISS1R expression (P < 0.001). Overexpression of full-length KISS1 in low KISS1-expressing PC-3M cells, but not KFMΔSS, which lacks the secretion signal sequence, induced re-sensitization of cells to anoikis, although it had no effect on either cell proliferation or apoptosis. Overexpression of KISS1 also suppressed steps in the metastatic cascade, including motility and invasiveness. Moreover, cells overexpressing KISS1 were found to enhance chemosensitivity to paclitaxel. Collectively, our data suggest that KISS1 functions as a metastasis suppressor in PCas and may serve as a useful biomarker as well as a therapeutic target for aggressive PCas.
对于美国男性而言，前列腺癌（PCa）是最常见的恶性肿瘤，也是癌症死亡的第二大主要原因。PCa 的转移扩散是导致大多数与 PCa 相关死亡的原因。尽管 KISS1 在多种癌症中作为转移抑制因子发挥作用，但它在 PCa 发展和进展中的表达水平和功能仍未确定。本研究的目的是将 KISS1 在 PCa 中的表达水平与临床病理特征相关联，并评估 KISS1 对 PCa 细胞活力和迁移能力的生物学相关性。在良性前列腺组织中检测到强烈的 KISS1 染色，但在原发性和转移性 PCa 中染色较弱（均 P < 0.001，t 检验）。此外，KISS1 在 PCa 中的低表达水平与临床分期（P < 0.01）和 KISS1R 表达（P < 0.001）相关。在低 KISS1 表达的 PC-3M 细胞中过表达全长 KISS1，但在缺乏分泌信号序列的 KFMΔSS 中没有，这会诱导细胞对失巢凋亡重新敏感，尽管这对细胞增殖或凋亡没有影响。KISS1 的过表达还抑制了转移级联中的多个步骤，包括迁移和侵袭。此外，发现过表达 KISS1 的细胞增强了对紫杉醇的化疗敏感性。总的来说，我们的数据表明 KISS1 在 PCa 中作为转移抑制因子发挥作用，并且可能作为侵袭性 PCa 的有用生物标志物和治疗靶标。
