Over expression of endoglin in human prostate cancer suppresses cell detachment, migration and invasion

Abstract

The regulation of cell adhesion and motility in human prostate is not well understood. We have previously shown that the endoglin gene is differently expressed during changes in prostate cell adhesion. Endoglin is a transmembrane transforming growth factor b binding protein typically expressed by endothelial cells. In this report we demonstrate that endoglin over expression increases prostate cell attachment, while decreasing migration and invasion. Engineered decreases in endoglin expression have opposite effects. While endoglin exerted only relatively small effects upon cell adhesion, large effects upon cell migration and invasion were observed. Endoglin was shown to localize to focal adhesion plaques, consistent with its role in regulating cell adhesion and motility. Loss of endoglin expression in cancer, as compared to normal prostate, was seen in human prostate cell lines. Suppression of endoglin expression in a panel of normal human prostate cell lines led to cell detachment. Endoglin is identified as a regulator of cell adhesion, motility and invasion in human prostate. Loss of endoglin expression appears to be associated with prostate cancer progression, at least in vitro.

Whole-mount prostate sections reveal differential endoglin expression in stromal, epithelial, and endothelial cells with the development of prostate cancer

“…Indeed, and although truly 'normal' prostates from young men (autopsy, organ donors) could not be processed as whole-mounts in our setting, the lack of staining in the normal/benign epithelium in the studied patient's population (91% of cases) is in agreement with the literature. 12,[14][15][16][17][18] On the other hand, observations on high endoglin-staining in epithelial cells of PIN lesions and tumors in these whole-mount sections, and often more intense in PIN than cancer within a specimen, are 20 While this may suggest a link with early phases of the disease, studies are underway to establish whether endoglin expression in prostate tumor cells is associated progression. Notably, in vitro studies in prostatic carcinoma cell lines indicate that endoglin exerts a function of its own linked to adhesion and migration/invasion.…”

“…Notably, endoglin expression has been reported in immortalized human prostate cells and prostate cancer cell lines and modifications in endoglin levels resulted in altered cell adhesion and migration/invasion. 19,20 Based on these findings and possible changes in the composition of TGF-b receptor complexes and hence tumor cell sensitivity to TGF-b in prostate cancer, 21 the objectives of this study were to test in whole-mount sections of human prostate: (1) whether endoglin protein expression in the stroma and epithelium differs with the onset of proliferative diseases and (2) whether assessment of blood vessels is similar between endoglin and von Willebrand Factor (vWF).…”

PRH/HHex inhibits the migration of breast and prostate epithelial cells through direct transcriptional regulation of Endoglin

“…Several studies have concluded that decreased Endoglin expression is associated with prostate cancer cell migration. For example, Endoglin expression was found to be lower in multiple cancer cell lines than in immortalised normal prostate cells and down-regulation of Endoglin expression was shown to increase prostate cancer cell migration and invasion (17). More recent data have shown that decreased Endoglin levels in prostate cancer cells result in increased metastasis and increased tumour size (18).…”

Characterization of a method for profiling gene expression in cells recovered from intact human prostate tissue using RNA linear amplification

“…With cell lines, microgram quantities of total RNA were extracted as described previously, 17 using Trizol reagent (Invitrogen, Carlsbad, CA, USA). RNA was treated with RNase-free DNase (Qiagen, Valencia, CA, USA), as per the manufacturer's instructions.…”

“…RNA quality and quantity was evaluated by measuring optical density (OD) 260/280, as well as by visual inspection of agarose gels, as described previously. 17 With prostate epithelial cells microdissected from intact human prostate tissue by LCM, nanogram quantities of total RNA were extracted using the PicoPure RNA Extraction kit (Arcturus, Mountain View, CA, USA) according to the manufacturer's instructions, with modifications. The first modification was that after RNA extraction buffer was added to microdissected tissue on the LCM cap, it was frozen on dry ice until a total of four LCM caps were completed.…”