Survivin expression and its relation with proliferation, apoptosis, and angiogenesis in brain gliomas

Abstract

BACKGROUND An unbalance of cell proliferation and cell apoptosis is an important mechanism in carcinogenesis, and angiogenesis also plays a crucial role in tumorigenesis. Recently, survivin has been identified as an important member of the inhibitor of apoptosis protein (IAP) family. Although it has been shown that survivin is highly expressed in gliomas, and is associated with tumorigenesis, progression, and poor prognosis of gliomas, as yet the relation of survivin expression with proliferation, apoptosis, and angiogenesis of gliomas it is still unclear. METHODS Eighty‐three cases of brain glioma were chosen and protein expressions of survivin and proliferating cell nuclear antigen (PCNA) in glioma cells and Factor VIII‐related antigen (FVIII‐RAg) in vascular endothelial cells were investigated by immunohistochemistry. Apoptotic cells of brain glioma were screened by TdT‐mediated dUTP nick end‐labeling (TUNEL), and survivin immunoreactivity score (IRS), proliferative index (PI), apoptotic index (AI), overall daily growth (ODG), and microvessel density (MVD) in brain gliomas were measured. RESULTS The survivin IRS, PI, AI, ODG, and MVD of brain gliomas were 3.75 ± 3.89, 28.39 ± 19.49%, 1.00 ± 0.80%, 12.19 ± 10.21%, and 62.75 ± 31.50, respectively, and all of them increased markedly with an increase in the pathologic grade of brain gliomas (P < 0.001 for all). PI, ODG, and MVD in the survivin‐positive group were significantly higher than those in the survivin‐negative group (P < 0.001 for all). PI, ODG, and MVD were positively correlated with survivin IRS (P < 0.001 for all). Although there was no significant difference between AI in the survivin‐positive group or in the survivin‐negative group (P = 0.108), AI was inversely correlated with survivin IRS (P = 0.005). CONCLUSIONS Survivin is overexpressed in brain gliomas, which may play an important role in malignant proliferation, antiapoptosis, and angiogenesis of brain gliomas. Cancer 2005. © 2005 American Cancer Society.

Increased Survivin Expression Confers Chemoresistance to Tumor-Associated Endothelial Cells

“…Because survivin is overexpressed in a variety of tumors including gliomas, 15 we wanted to explore whether survivin is also overexpressed in the tumor vasculature. To accomplish this, we immunostained cell preparations of TuBECs and BECs with an antibody to survivin.…”

“…13 In various tumors, high survivin levels are correlated with poor prognosis, decreased apoptosis, increased angiogenesis, and chemoresistance in cancer cell lines. 14,15 However, little is known of survivin's function in the endothelial cells of the tumor vasculature.…”

Hyperthermia increases the therapeutic efficacy of survivinT34A in mouse tumor models

“…2 It is widely expressed in a strictly regulated manner during embryonic development but rarely detected in normal tissues. 3 By contrast, survivin is prominently overexpressed in most malignant tumors, especially in colon cancer, such as SW480, HCT116 and CT26 and so on.…”

Adeno-associated virus-mediated survivin mutant Thr34Ala cooperates with oxaliplatin to inhibit tumor growth and angiogenesis in colon cancer

“…Several studies have shown that the elevated survivin expression is associated with increased microvessel density in colorectal cancer (9), colon cancer (23) and brain glioma (33). Increased survivin expression has been verified in endothelial cells during the proliferative (25,34,35) and remodeling (36,37) phases of angiogenesis, potentially serving as a cytoprotective mechanism for these cells (35).…”

“…Importantly, induction of survivin in endothelial cells is associated with resistance to apoptosis. In contrast, survivin is undetectable in quiescent endothelium in vitro and in vivo (25), and targeting survivin does not affect endothelial cell viability in quiescent endothelium (33). Thus, inhibition of survivin may promote endothelial cell apoptosis during tumor angiogenesis, accelerating regression of newly formed blood vessels and reducing the incidence of metastatic disease.…”