Overexpression of clusterin promotes angiogenesis via the vascular endothelial growth factor in primary ovarian cancer

Abstract

Clusterin (CLU), a multifunctional glycoprotein, is ubiquitously produced in mammalian tissues. CLU has been shown to play significant roles in many of the biological behaviours of human tumors, such as cell proliferation, apoptosis, chemoresistance and angiogenesis. However, the relationship of CLU expression with angiogenesis in ovarian cancer has not been studied. A total of 275 epithelial ovarian tumors were obtained from archives of paraffin‑embedded tissues. Immunohistochemical (IHC) staining for CLU and vascular endothelial growth factor (VEGF) was performed on a tissue microarray (TMA) including 181 primary ovarian epithelial cancer, 40 borderline ovarian tumors and 54 ovarian cancer mesenteric metastasis samples. Of the 174 cases, overexpression of CLU and VEGF were detected in 107 (61.5%) and 109 (62.9%) cases of primary ovarian carcinoma, respectively. Of the 107 cases of primary ovarian carcinoma with overexpression of CLU, expression of VEGF was increased in 82 (75.2%) cases. However, in another 67 cases without CLU overexpression, overexpression of VEGF was observed in only 27 (24.8%) cases (P<0.05). Overexpression of CLU in epithelial ovarian cancer appears to be correlated with increased tumor angiogenesis, consistent with the established role of CLU as an oncogene in the biology of ovarian cancer. In the treatment of ovarian cancer, these two markers may be used in the selection of patients for targeted therapy.

Comparative multidimensional molecular analyses of pediatric diffuse intrinsic pontine glioma reveals distinct molecular subtypes

“…CLU is a secreted molecular chaperone protein implicated in cancer [15,17,31,42,54,55] that we previously detected in the CSF proteome of DIPG patients [43]. TLN1 is a cytoskeletal protein that controls integrin activation to facilitate cell migration by promoting cell motility and adhesion in glioma [7,40,41,46,56].…”

Exosomal clusterin, identified in the pericardial fluid, improves myocardial performance following MI through epicardial activation, enhanced arteriogenesis and reduced apoptosis

“…Overexpression of clusterin in epithelial ovarian cancer has been shown to correlate with increased tumor angiogenesis [40]. To assess whether clusterin enhanced vessel growth in the mouse model of acute MI, neoangiogenesis was evaluated in the left ventricle of clusterin treated infarcted heart, 1 week after MI.…”

Clusterin: a key player in cancer chemoresistance and its inhibition

“…14–18 sCLU depletion activates p53 and alters the ratio of proapoptotic to antiapoptotic Bcl-2 protein family members, triggering mitochondrial dysfunction and apoptosis. However, Bcl-2 suppression is a p53-independent effect, such that knockdown of p53 only minimally suppressed cell death, but a pan-caspase inhibitor completely avoided cell death.…”