Nestin: A novel angiogenesis marker and possible target for tumor angiogenesis

Abstract

Abnormal vasculature, termed tumor vessels, is a hallmark of solid tumors. The degree of angiogenesis is associated with tumor aggressiveness and clinical outcome. Therefore, exact quantification of tumor vessels is useful to evaluate prognosis. Furthermore, selective detection of newly formed tumor vessels within cancer tissues using specific markers raises the possibility of molecular targeted therapy via the inhibition of tumor angiogenesis. Nestin, an intermediate filament protein, is reportedly expressed in repair processes, various neoplasms, and proliferating vascular endothelial cells. Nestin expression is detected in endothelial cells of embryonic capillaries, capillaries of the corpus luteum, which replenishes itself by angiogenesis, and proliferating endothelial progenitor cells, but not in mature endothelial cells. Therefore, expression of nestin is relatively limited to proliferating vascular endothelial cells and endothelial progenitor cells. Nestin expression is also reported in blood vessels within glioblastoma, prostate cancer, colorectal cancer, and pancreatic cancer, and its expression is more specific for newly formed blood vessels than other endothelial cell markers. Nestin-positive blood vessels form smaller vessels with high proliferation activity in tumors. Knockdown of nestin in vascular endothelial cells suppresses endothelial cell growth and tumor formation ability of pancreatic cancers in vivo. Using nestin to more accurately evaluate microvessel density in cancer specimens may be a novel prognostic indicator. Furthermore, nestin-targeted therapy may suppress tumor proliferation via inhibition of angiogenesis in numerous malignancies, including pancreatic cancer. In this review article, we focus on nestin as a novel angiogenesis marker and possible therapeutic target via inhibition of tumor angiogenesis.

Numerical impairment of nestin+ bone marrow niches in acute GvHD after allogeneic hematopoietic stem cell transplantation for AML

“…After cellular differentiation, nestin is downregulated and replaced by a tissue-specific intermediate filament, such as neurofilaments in neurons and desmin in muscles; nestin is therefore thought to be a neuronal stem cell marker. [16][17][18][19] In adult organisms, nestin-expressing cells are restricted mainly to defined areas of regeneration, where they function as a cellular reserve capable of proliferation, differentiation and migration after reactivation. 19,20 In the BM, the nestin + mesenchymal stem cells innervated by sympathetic nerve fibers regulate normal HSCs, and sympathetic innervation rescues nestin + mesenchymal stem cells from apoptosis.…”

Nestin expression as an independent indicator of poor prognosis for patients with anaplastic thyroid cancer

“…The acceleration of cancer cell proliferation, invasive growth and migration have previously been reported to correlate with nestin expression in several cancer types (22)(23)(24). These features are cellular mechanisms underlying cancer progression and metastasis, and they are also common characteristics found in ATC cells.…”

Proliferation and maturation of intratumoral blood vessels in women with malignant ovarian tumors assessed with cancer stem cells marker nestin and platelet derived growth factor PDGF-B

“…Nestin has been reported to correlate with aggressive growth, metastasis, and poor prognosis in several malignancies; however, the role of nestin in ovarian cancer neoangiogenesis has not been well characterized [8,11,14,15]. Compared to MVD studies that used several panendothelial markers, only a limited number of investigations have employed nestin.…”

“…One of the novel markers of the proliferating endotheliocytes is nestin -an intermediate filament protein, initially thought to be exclusively associated with neuro-progenitor cells [8][9][10]. Although nestin is expressed during early stages of normal cells development, under pathological conditions this protein could be also found in cancer stem cells, as well as in perivascular and endothelial cells suggesting its role in various malignant tumors neoangiogenesis [11,12].…”