Richardson Annely M, Woodson Karen, Wang Yonghong, Rodriguez-Canales Jaime, Erickson Heidi S, Tangrea Michael A, Novakovic Kristian, Gonzalez Sergio, Velasco Alfredo, Kawasaki Ernest S, Emmert-Buck Michael R, Chuaqui Rodrigo F, Player Audrey
Pathogenetics Unit, National Cancer Institute at Frederick, Frederick, MD, USA.
Diagn Mol Pathol. 2007 Dec;16(4):189-97. doi: 10.1097/PDM.0b013e3180de20ac.
Characterization of gene expression profiles in tumor cells and the tumor microenvironment is an important step in understanding neoplastic progression. To date, there are limited data available on expression changes that occur in the tumor-associated stroma as either a cause or consequence of cancer. In the present study, we employed a 54,000 target oligonucleotide microarray to compare expression profiles in the 4 major components of the microenvironment: tumor epithelium, tumor-associated stroma, normal epithelium, and normal stroma. Cells from 5 human, whole-mount prostatectomy specimens were microdissected and the extracted and amplified mRNA was hybridized to an Affymetrix Human Genome U133 Plus 2.0 GeneChip. Using the intersection of 2 analysis methods, we identified sets of differentially expressed genes among the 4 components. Forty-four genes were found to be consistently differentially expressed in the tumor-associated stroma; 35 were found in the tumor epithelium. Interestingly, the tumor-associated stroma showed a predominant up-regulation of transcripts compared with normal stroma, in sharp contrast to the overall down-regulation seen in the tumor epithelium relative to normal epithelium. These data provide insight into the molecular changes occurring in tumor-associated stromal cells and suggest new potential targets for future diagnostic, imaging, or therapeutic intervention.
肿瘤细胞和肿瘤微环境中基因表达谱的表征是理解肿瘤进展的重要一步。迄今为止，关于肿瘤相关基质中作为癌症原因或结果而发生的表达变化的数据有限。在本研究中，我们采用了一种含有54,000个靶标的寡核苷酸微阵列，以比较微环境的4个主要成分中的表达谱：肿瘤上皮、肿瘤相关基质、正常上皮和正常基质。对5例人类全前列腺切除标本中的细胞进行显微切割，并将提取和扩增的mRNA与Affymetrix人类基因组U133 Plus 2.0基因芯片杂交。使用两种分析方法的交集，我们在这4个成分中鉴定出差异表达基因集。发现44个基因在肿瘤相关基质中持续差异表达；35个在肿瘤上皮中被发现。有趣的是，与正常基质相比，肿瘤相关基质显示出转录本的主要上调，这与肿瘤上皮相对于正常上皮总体下调形成鲜明对比。这些数据为肿瘤相关基质细胞中发生的分子变化提供了见解，并为未来的诊断﹑成像或治疗干预提出了新的潜在靶点。
