Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
APMIS. 2012 Jul;120(7):558-71. doi: 10.1111/j.1600-0463.2011.02865.x. Epub 2012 Jan 25.
Prostate cancer is the most common type of cancer in men. It is assumed that the tumor microenvironment of the prostate contributes to invasion and metastasis. Stroma-epithelial crosstalk has shown to change with progression of prostate cancer, and thereby the stromal compartment might be an attractive target in diagnostic and therapeutic approaches to prostate cancer. The purpose of this project was to study the reciprocal influence between fibroblasts and cancer cells in prostate cancer. Prostate fibroblast primary cultures from areas with cancer and hyperplasia were cocultivated with cells of the PC-3 lineage. Gene expression profiles of both cell types were studied to reveal possible associations to cancer invasion and metastasis. There were 383 differentially expressed genes between fibroblasts from cancerous areas and fibroblasts from areas with hyperplasia before cocultivation with PC-3 cells. Several of the differentially expressed gene classes are associated with cancer development and metastasis. After cocultivation, there were 26 differentially expressed genes between cancerous and hyperplastic fibroblasts. There were only three differentially expressed genes between PC-3 cells that had been cocultivated with cancerous fibroblasts and PC-3 cells that had been cocultivated with hyperplastic fibroblasts. The fibroblasts from cancer areas showed a different expression pattern from the characteristics reported as reactive stroma in previous studies. We found tenascin C to be downregulated, which is contrary to previous findings. TGF-β3 and TGF-βR3 were also downregulated, which has been associated with disturbance of TGF-β signaling during prostate cancer progression. Cocultivation with PC-3 cells seems to make the cancerous and hyperplastic fibroblasts more alike each other, as the number of differentially expressed genes decreases. It is desirable to find out if the reduction in differential gene expression is attributable to that hyperplastic fibroblasts become more alike the cancerous fibroblasts or vice versa. Also, we think that the lower expression levels of c-Jun and c-Fos in cancerous fibroblasts without coculture may cause loss of normal fibroblast differentiation, proliferation and inflammatory response, and hence, favor the proliferation and invasion of cancer cells.
前列腺癌是男性最常见的癌症类型。据推测，前列腺的肿瘤微环境有助于肿瘤的侵袭和转移。研究表明，前列腺癌进展过程中，基质-上皮细胞的相互作用会发生改变，因此基质细胞可能是前列腺癌诊断和治疗方法的一个有吸引力的靶点。本项目旨在研究前列腺癌中成纤维细胞和癌细胞之间的相互影响。将来自癌症和增生区域的前列腺成纤维细胞原代培养物与 PC-3 细胞系进行共培养。研究两种细胞类型的基因表达谱，以揭示可能与癌症侵袭和转移相关的关联。在与 PC-3 细胞共培养之前，来自癌症区域的成纤维细胞和来自增生区域的成纤维细胞之间有 383 个差异表达基因。几个差异表达的基因类别与癌症发展和转移有关。共培养后，来自癌症和增生区域的成纤维细胞之间有 26 个差异表达基因。与癌症成纤维细胞共培养的 PC-3 细胞和与增生成纤维细胞共培养的 PC-3 细胞之间只有三个差异表达基因。来自癌症区域的成纤维细胞表现出与之前研究中报道的反应性基质不同的表达模式。我们发现层粘连蛋白 C 下调，这与之前的发现相反。TGF-β3 和 TGF-βR3 也下调，这与前列腺癌进展过程中 TGF-β 信号通路的紊乱有关。与 PC-3 细胞共培养似乎使癌症和成纤维细胞彼此更相似，因为差异表达基因的数量减少。希望了解差异基因表达的减少是否归因于增生成纤维细胞变得更类似于癌症成纤维细胞，或者反之亦然。此外，我们认为，没有共培养的癌症成纤维细胞中 c-Jun 和 c-Fos 的低表达可能导致正常成纤维细胞分化、增殖和炎症反应的丧失，从而有利于癌细胞的增殖和侵袭。
