CXCR4 is highly expressed at the tumor front but not in the center of prostate cancers

• Published in: World journal of urology Vol. 33; no. 2; pp. 281 - 287
• Main Authors: Delongchamps, Nicolas Barry, Beuvon, Frédéric, Mathieu, Jacques R. R., Delmas, Stéphanie, Metzger, Isabelle, Prats, Hervé, Cabon, Florence
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-02-2015; Springer Nature B.V
• Subjects: Aged; beta Catenin - biosynthesis; Biomarkers, Tumor - biosynthesis; Cadherins - biosynthesis; Cell Movement; Chemokine CXCL12 - biosynthesis; Humans; Male; Medicine; Medicine & Public Health; Middle Aged; Nephrology; Oncology; Original Article; Prognosis; Prostatectomy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Prostatic Neoplasms - surgery; Receptors, CXCR4 - biosynthesis; RNA, Messenger - biosynthesis; Urology; Local invasion; SDF-1; CXCR4; β-Catenin; Prostate cancer; Tumor front; E-cadherin
• ISSN: 0724-4983; 1433-8726
• DOI: 10.1007/s00345-014-1299-0

Objective
To evaluate the expression of CXCR4, its ligand SDF-1, β-catenin and E-cadherin throughout the local tumor microenvironment of prostate cancer.
Patients and methods
A total of 64 prostate cancer specimens, 24 frozen and 40 paraffin-embedded sections, were obtained from patients treated with radical prostatectomy for clinically localized cancer. Real-time RT-PCR was used for mRNA quantification of CXCR4 and SDF-1 in the tumor center (T), tumor front (F) and distant peritumoral tissue (D). Immunohistochemical analysis was used to investigate the expression patterns of CXCR4, E-cadherin and β-catenin. Clinical records of these patients were studied for follow-up data, and the prognostic value of these molecules’ expression was statistically assessed.
Results
CXCR4 mRNA and protein were significantly increased at the tumor front as compared to distant tissue or tumor center. In comparison, SDF-1 mRNA level gradually increased from the tumor center to the distant peritumoral tissue. High CXCR4 at the tumor front was associated with high Gleason score. Low SDF-1 at the tumor front was associated with locally advanced cancer and disease recurrence. Moreover, high CXCR4 staining at the tumor front and increased cytosolic E-cadherin expression in the same location was associated with locally advanced disease.
Conclusions
CXCR4 seems overexpressed at the tumor front of prostate tumors, where it potentially promotes cell migration toward the SDF-1 centrifugal attracting gradient, as well as epithelial–mesenchymal transition. High CXCR4 and low SDF-1 levels at tumor front were both associated with adverse histological features.