Identification of neovasculature using nestin in colorectal cancer

Abstract

Abstract. CD34 is commonly used as an endothelial cell marker of tumor vessels. However, this marker detects not only newly formed, but also pre-existing large blood vessels. Nestin, a class VI intermediate filament protein, has recently received attention as a marker for detecting newly formed endothelial cells. In this study, whether nestin is a novel angiogenesis marker in colorectal cancer was examined. HCT-15, a human colon cancer cell line, was subcutaneously implanted into the dorsum of nude mice. After the tumor grew, the mice were perfused with fluorescent beads (Fluospheres). Then, the tumor tissues were used for immunofluorescence staining using nestin and the CD34 antibody. Immunohistochemistry was performed with nestin and CD34 on 101 human colorectal cancer tissue samples. Proliferating endothelial cells were detected immunohistochemically by a proliferating cell nuclear antigen (PCNA) antibody. Clinicopathological factors and prognosis were compared between two groups: that with a microvessel density (MVD) higher than the median MVD and that with MVD lower than the median MVD, as detected by nestin and CD34 labellings. Nestin was localized in endothelial cells in small blood vessels (median, 9.06 μm), whereas CD34 was localized in large blood vessels (median, 9.67 μm) in nude mice. The diameter of nestin-positive vessels was smaller than that of CD34-positive vessels in human colorectal cancer. The number ratio of PCNA-positive cells to nestin-positive vascular endothelial cells was higher than that of PCNA-positive to CD34-positive cells (p=0.002). There were no correlations between nestin-positive blood vessels and clinicopathological factors, but the prognosis was worse in the highly nestin-positive MVD group (p=0.071). Nestin is considered a novel angiogenesis marker of proliferating endothelial cells in colorectal cancer tissue.

High Ki67, Bax, and thymidylate synthase expression well correlates with response to chemoradiation therapy in locally advanced rectal cancers: proposal of a logistic model for prediction

“…Similarly, Bax overexpression has been found to correlate with anticancer drug sensitivity in a variety of human cancers, through enhanced induction of apoptosis (Krajewski et al, 1995;Guo et al, 2000;Teranishi et al, 2007). However, Gosens et al (2008) did not find any link between Bax expression and rectal cancer regression for neoadjuvant chemoradiation.…”

“…Nestin-examined capillaries were considered as capillaries consisting of newly formed endothelial cells (Teranishi et al, 2007). Areas of highest neovascularisation were found by scanning tumour sections at low power ( Â 100).…”

“…It has been also reported that VEGF-positive rectal cancer was resistant to radiotherapy (Zlobec et al, 2008). Nestin, a class VI intermediate filament protein, has recently received attention as a marker for detecting newly formed endothelial cells (Teranishi et al, 2007).…”

Assessment of angiogenesis by CD105 and nestin expression in peritumor tissue of glioblastoma

“…Five hot spot fields were counted and the average was regarded as the MVD of that section (30). CD105-MVD was evaluated in both tumor and peritumor tissue.…”

Prognostic Significance of Nestin Expression in pT1 High-Grade Bladder Urothelial Carcinoma Patients Treated with Intravesical BCG

“…Increased nestin expression has also been reported in various tumor cells, especially in central nervous system and gastrointestinal tumors as a poor prognostic factor (Eaker and Sallustio., 1994;Toshiyuki et al, 2011). High expression levels in tumor blood vessels and proliferating endothelial cells in certain tumor types suggest a relationship between tumor angiogenesis and nestin (Kim et al, 2002;Teranishi et al, 2007;Gravdal et al, 2009;Eaton et al, 2010). From urological point of view, reduction of nestin expression has been shown to be correlated with decreased invasion and migration capability of prostate cancer cells (Gravdal et al, 2009).…”