Role of nestin expression in angiogenesis and breast cancer progression

Abstract

Nestin is an intermediate filament protein and a stem cell marker expressed in several tumours. There is growing evidence of an association between the expression level of nestin and the pathogenesis of triple-negative breast cancer (TNBC). Nestin is also expressed in newly forming tumour vessels and is a valuable marker of ongoing angiogenesis. In this study, we aimed to evaluate the prognostic value of nestin expression in breast tumour cells and to determine whether this expression influences angiogenesis. Immunohistochemical (IHC) analyses were carried out on 124 cases of invasive ductal carcinoma (IDC) of the breast with a panel of murine monoclonal antibodies against nestin, CD31, CD34, SOX-18 and Ki‑67. We evaluated nestin expression in tumour and endothelial cells, Ki‑67 in tumour cells, and CD31, CD34 and SOX-18 in endothelial cells. Our results demonstrated that nestin expression in tumour cells correlated with the area and number of vessels expressing nestin, CD31, CD34 and SOX-18. We also found a positive correlation between nestin-expressing vessels and SOX-18-expressing vessels. Our results are consistent with those of previous studies, in which nestin expression in endothelial cells was shown to be strongly associated with triple-negative subtype, poorly differentiated G3 tumours, a higher proliferation index and a shorter overall survival. Nestin expression was also examined in human breast cancer cell lines (MCF-7, SK-BR-3, MDA‑MB‑231 and BO2 cells) representing a different level of tumour aggressiveness and reflecting histological grade. A higher nestin protein level was observed in more aggressive MDA‑MB‑231 and BO2 cells than in MCF-7 and SK-BR-3 cells.

The prognostic relevance of FOXA1 and Nestin expression in breast cancer metastases: a retrospective study of 164 cases during a 10-year period (2004–2014)

“…Nestin might participate in neovascularization through cytoskeletal changes promoted by the interaction between cancer cells with stem cell properties and endothelial cells lining blood vessels in the tumor stroma. Nowak et al reported that Nestin expression in endothelial cells lining newly formed breast tumor-associated blood vessels was shown to be associated with the triple-negative subtype, lymph node metastases and shorter overall survival [17, 20]. Nestin contributes to activation of the EMT pathway by regulating the Wnt/β-catenin pathway [21] and may therefore play a role not only in the regulation of mitosis, but in tumor invasiveness [18].…”

Comparison of Microvessel Density Using Nestin and CD34 in Colorectal Cancer

“…As there are no unambiguous results, there is a need to search for more sensitive markers for the evaluation of angiogenesis in CRC. Taking into account the results of previous studies (18,19), we suggest nestin as a new biomarker for angiogenesis assessment in patients with CRC.…”

“…Nestin, a protein of the intermediate filaments of the cytoskeleton, appears to be more specific marker for newly formed blood vessels (17)(18)(19). Initially, nestin expression was reported in neuroepithelial stem cells, but further studies revealed its presence in many other progenitor cells i.e.…”

“…Reports in the literature shows that nestin is a reliable marker of newly formed tumour vessels, which also has potential clinical implications (24). A higher nestin-positive microvessel density (MVD) is associated with more aggressive cancer progression and poorer prognosis (18,19).…”

Implications of nestin in breast cancer pathogenesis (Review)

“…However, the high number of nestinexpressing cases (14/16) among the TNBCs and the lack of expression reported in luminal (0/16) and HER2-positive (0/16) tumours suggested that nestin may be an important marker of BC differentiation. Further studies confirmed the clinical implications of nestin expression in TNBC and basallike tumours (34,55,(90)(91)(92)(93)(94)(95)(96)(97). Parry et al (90), in an IHC study of 245 human invasive BC cases, demonstrated that nestin expression in tumour cells was predominantly observed in basal-like tumours, as defined by the IHC panel proposed by Nielsen et al (23).…”