Reelin expression in human prostate cancer: a marker of tumor aggressiveness based on correlation with grade

Abstract

Reelin is a glycoprotein that plays a critical role in the regulation of neuronal migration during brain development and, since reelin has a role in the control of cell migration, it might represents an important factor in cancer pathology. In this study, 66 surgical specimens of prostate cancer were analyzed for reelin expression by immunohistochemical method. The reelin expression was correlated with Gleason score and individual Gleason patterns. Reelin expression was found in 39% prostate cancers. Stromal tissues, normal epithelial cells and prostate intraepithelial neoplasia (PIN) of any grade around and distant from cancer were always negative for reelin. Reelin was found in malignant prostatic epithelial glands of 50% cases Gleason score 10, 52% Gleason score 9, 56% Gleason score 8, 18% Gleason score 7, while no sample of prostate cancers with Gleason score 6 showed reelin expression (P ¼ 0,005). As reelin staining is frequently found in high Gleason score prostate cancers, we explored whether reelin expression is influenced by single Gleason patterns. While Gleason 3 pattern did not show reelin immunoreactivity, reelin expression was found in 35% Gleason 4 patterns and 45% Gleason 5 patterns (Po0.001). Our results demonstrated for the first time that reelin is expressed in prostate cancer and not in benign prostate tissue and its expression occurs in higher Gleason score and correlates significantly with increasing of single Gleason patterns. This suggests reelin may behave as a specific histological marker and may represent a useful biomarker to predict aggressive phenotypic behavior of prostatic cancer cells.

MiR‐128 up‐regulation inhibits Reelin and DCX expression and reduces neuroblastoma cell motility and invasiveness

“…In general, no studies have been performed that link Reelin and neuroblastoma, while it is already known that this protein is modulated in other cancer types (25)(26)(27)41) in the majority of which, Reelin expression is directly correlated with tumor aggressiveness (25)(26)(27). The present findings support the existence of another mechanism through which miR-128 reduces neuroblastoma cell motility and invasiveness, i.e., by reducing Reelin protein levels.…”

“…However, the expression of this protein is not restricted to the CNS, as it has been found in some adult peripheral tissues and tumors. For example, Reelin has been shown to be a positive marker for prostate carcinoma aggressiveness (25) and is overexpressed in retinoblastoma (26) and esophageal carcinoma (27).…”

Epigenetic silencing of RELN in gastric cancer

“…High expression of RELN was reported in 87.5% of esophageal cancers (28) and in 39% of prostate cancers (29). Conversely, the expression of RELN was reported to be only focal or completely absent in 72% of pancreatic cancers in which the RELN promoter was hypermethylated (14).…”

A Prominent Couple

“…Reelin, commonly secreted by Cajal-Retzius cells in the developing nervous system, is increased in small cell lung cancer, retinoblastoma, esophageal cancer and multiple myeloma [105][106][107][108]. In PCa, a correlation between Reelin expression and Gleason score has been described [109]. However, the molecular mechanisms of Reelin signaling in the aggressiveness of PCa is yet unknown.…”

“…IL-6 triggered REST repression and STAT3-induced NED in LNCaP cells [106][107][108]. Neuropeptides and IL-8 activated the nonreceptor tyrosine kinases ETK, Src and FAK resulting in androgenindependent AR activation [100,109]. In a transgenic adenocarcinoma of the mouse prostate (TRAMP) model, cooperativity between the NE-specific forkhead transcription factor FoxA2 and the hypoxia-induced transcription factor HIF1α induced target genes that were required for a NE phenotype in PCa [110].…”