School of Medicine, University of Cartagena, Cartagena, Colombia.
Research Group of Genetics and Molecular Biology, Colombia.
Cancer Biomark. 2016;16(1):191-202. doi: 10.3233/CBM-150555.
Fibromodulin is a small leucine-rich proteoglycan important for extracellular matrix organization and essential for tissue repair in multiple organs. The main function of this proteoglycan is the regulation of collagen fibrillogenesis; however, more recently described roles for fibromodulin have expanded to include regulation of angiogenesis, reprogramming of human fibroblasts into pluripotent cells, modulation of TGF-β activity, inflammatory processes and association with metastatic phenotypes. Additionally, fibromodulin has been identified as a novel tumor-associated antigen in leukemia, lymphoma, and leiomyoma. Knowledge about its expression in the prostate is limited.
Fibromodulin expression was analyzed in two different malignant and one non-tumorigenic prostatic cell lines in culture, and in benign and malignant human prostate tissue. Expression was analyzed by real time PCR, immunocytochemistry, and immunohistochemistry. DNA sequencing was performed on a PCR fragment amplified with primers specific for the FMOD gene from cDNA obtained from the cultured cell lines.
Both immunostaining and real time PCR analysis of cell lines indicated that fibromodulin was differentially expressed in the cancerous cell lines compared to the non-tumorigenic cell line. Likewise, cancerous tissue expressed significantly higher levels of intracellular fibromodulin compared to matched, benign tissue from the same patients, as well as compared to tissue from patients with only benign disease.
The expression of fibromodulin was higher in prostatic cancer cells (cell-lines and human tissue) than in normal/benign prostatic cells. Additional studies are required to determine the biological and clinical significance and whether this proteoglycan has a role in carcinogenesis of the prostate or in prostate cancer related inflammatory processes.
纤维调蛋白是一种富含亮氨酸的小蛋白聚糖,对细胞外基质的组织和多个器官的组织修复至关重要。该蛋白聚糖的主要功能是调节胶原纤维原纤维的形成;然而,最近描述的纤维调蛋白的作用已扩展到包括调节血管生成、将人成纤维细胞重编程为多能细胞、调节 TGF-β 活性、炎症过程以及与转移表型的关联。此外,纤维调蛋白已被确定为白血病、淋巴瘤和平滑肌瘤中的一种新型肿瘤相关抗原。关于其在前列腺中的表达的知识有限。
在两种不同的恶性和一种非肿瘤前列腺细胞系中以及在良性和恶性人前列腺组织中分析纤维调蛋白的表达。通过实时 PCR、免疫细胞化学和免疫组织化学分析表达。从培养的细胞系获得的 cDNA 用针对 FMOD 基因的引物扩增 PCR 片段后,进行 DNA 测序。
细胞系的免疫染色和实时 PCR 分析均表明,与非肿瘤细胞系相比,纤维调蛋白在癌细胞系中差异表达。同样,与来自同一患者的匹配良性组织相比,与仅患有良性疾病的患者的组织相比,癌组织中细胞内纤维调蛋白的表达水平显着更高。
纤维调蛋白在前列腺癌细胞(细胞系和人类组织)中的表达高于正常/良性前列腺细胞。需要进一步研究以确定其生物学和临床意义,以及该蛋白聚糖是否在前列腺癌发生或与前列腺癌相关的炎症过程中起作用。