Extracellular matrix associated protein CYR61 is linked to prostate cancer development.
OBJECTIVE
The cancer cell microenvironment includes complex interactions between the cell and the extracellular matrix. Expression of the CCN family of extracellular matrix associated proteins is often modified in disease states. Depending on cancer type these changes are linked with enhanced or inhibited tumor growth. We characterized Cyr61 in prostate cancer. Cyr61 is an integrin binding matricellular protein with altered expression in many cancer types.


METHODS
Cyr61 expression in prostate cancer, benign prostatic hyperplasia and normal tissues was evaluated by microarray analysis, quantitative real-time polymerase chain reaction and tissue microarray. Immunoblots were analyzed to assess endogenous protein expression in prostate cancer cell lines.


RESULTS
On genomic analysis Cyr61 up-regulation was observed in prostate cancer tissue and in normal prostate tissue adjacent to tumor vs that in prostate donor tissue. In 174 matched tumors and normal prostate tissues adjacent to tumor tissue microarray revealed significantly up-regulated Cyr61 protein expression in cancer tissue vs normal prostate tissue adjacent to tumor. Also, increased Cyr61 expression correlated with Gleason sum 8 or greater cancer. Staining in high grade prostatic intraepithelial neoplasia was moderately up-regulated vs that in normal prostate tissue adjacent to tumor but generally less intense than in carcinoma tissue.


CONCLUSIONS
In addition to the correlation with more advanced disease, the strong association between Cyr61 expression and prostate cancer supports the potential usefulness of Cyr61 as a novel biomarker for prostate cancer. This warrants further analysis to determine the mechanisms by which Cyr61 may contribute to prostate cancer development and progression.
D'Antonio
Katherine B
KB
The Brady Urological Institute, Baltimore, Maryland 21287, USA.
Toubaji
Antoun
A
Albadine
Roula
R
Mondul
Alison M
AM
Platz
Elizabeth A
EA
Netto
George J
GJ
Getzenberg
Robert H
RH
D000328:Adult; D000368:Aged; D055515:Cysteine-Rich Protein 61 / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000209:etiology*
C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61