Stem-Like Ovarian Cancer Cells Can Serve as Tumor Vascular Progenitors

Abstract

Neovascularization is required for solid tumor maintenance, progression, and metastasis. The most described contribution of cancer cells in tumor neovascularization is the secretion of factors, which attract various cell types to establish a microenvironment that promotes blood vessel formation. The cancer stem cell hypothesis suggests that tumors are composed of cells that may share the differentiation capacity of normal stem cells. Similar to normal stem cells, cancer stem cells (CSCs) have the capacity to acquire different phenotypes. Thus, it is possible that CSCs have a bigger role in the process of tumor neovascularization. In this study, we show the capacity of a specific population of ovarian cancer cells with stem-like properties to give rise to xenograft tumors containing blood vessels, which are lined by human CD341 cells. In addition, when cultured in high-density Matrigel, these cells mimic the behavior of normal endothelial cells and can form vessel-like structures in 24 hours. Microscopic analysis showed extensive branching and maturation of vessel-like structures in 7 days. Western blot and flow cytometry analysis showed that this process is accompanied by the acquisition of classic endothelial markers, CD34 and VEcadherin. More importantly, we show that this process is vascular endothelial growth factor-independent, but IKKb-dependent. Our findings suggest that anti-angiogenic therapies should take into consideration the inherent capacity of these cells to serve as vascular progenitors.

Oct-4+/Tenascin C+ neuroblastoma cells serve as progenitors of tumor-derived endothelial cells

“…The same group has demonstrated that breast cancer stem/progenitor cells are capable of differentiating into TECs [9]. Likewise, Alvero et al [57] have shown that TECs may originate from a subset of ovarian cancer cells with a highly angiogenic phenotype and the features of cancer stem cells. The connection between neural stem cells and the endothelial compartment seems to be critical in glioblastoma, where cancer stem cells closely interact with the vascular niche and promote angiogenesis [58].…”

Hinokitiol inhibits vasculogenic mimicry activity of breast cancer stem/progenitor cells through proteasome-mediated degradation of epidermal growth factor receptor

“…CD44 + type I epithelial ovarian cancer cells have been demonstrated to form vascular structures when cultured in Matrigel conditions in vitro and to transdifferentiate into CD34 + endothelial progenitor cells (35). The progeny of glioma CSCs cultured in endothelial conditions have previously exhibited features of functional endothelial cells (36).…”

TRX-E-002-1 Induces c-Jun–Dependent Apoptosis in Ovarian Cancer Stem Cells and Prevents Recurrence In Vivo

“…These patient samples were obtained from patients at Yale New Haven Hospital (New Haven, CT) who were diagnosed with stage III/IV serous ovarian cancer and propagated as described previously (9,10,14,(28)(29)(30)(31)(32)(33) …”