Increased Resistance of Vasculogenic Mimicry-Forming Uveal Melanoma Cells against Cytotoxic Agents in Three-Dimensional Cultures

Abstract

Purpose Cancer stem cells have increased resistance against a variety of anti-tumor treatment modalities. Vasculogenic mimicry (VM) patterns are present in numerous malignant tumor types, represent the formation of perfusion pathways by tumor cells, and their presence in tumors is associated with adverse outcome. Earlier we have shown that VM-forming tumor cells in three-dimensional (3D) uveal melanoma cultures have increased resistance against cytotoxic agents and oncolytic herpes simplex virus-mediated destruction. The purpose of the current study was to explore the possibility that this increased resistance of VM-forming tumor cells is due to a cancer stem cell phenotype. Methods The expression of cancer stem cell marker cluster of differentiation 271 (CD271) was determined in traditional two-dimensional (2D) and 3D cultures of C918 uveal melanoma cells by fluorescent immunocytochemistry. Results We found that the VM-forming tumor cell subpopulation in 3D cultures expressed CD271. In contrast, cells grown in 2D cultures and tumor cell subpopulations not participating in VM formation in 3D cultures were negative for CD271. Conclusions These findings suggest that VM-forming uveal melanoma cells acquire a cancer stem cell-like phenotype that may play a role in the increased therapy resistance of these cells.

Aberrant Expression of Markers of Cancer Stem Cells in Gastric Adenocarcinoma and their Relationship to Vasculogenic Mimicry

“…Furthermore, more and more evidence supports the conception that the markers of CSCs expression are not only significantly associated with VM formation and transdifferentiation into endothelial cells, but also associated with more rapid tumor growth and metastasis. Our study is consistent with these researches (Valyi-Nagy et al, 2012;Liu et al, 2013;Yao et al, 2013). We speculated that the VM might provide the sufficient nutrition and oxygen to promote the tumor growth and metastasis after the nutrition and oxygen supplied by neovascularization could not meet the needs of tumor growth.…”

Three‑dimensional cell culture: A powerful tool in tumor research and drug discovery (Review)

“…CSC research using Matrigel has also been performed. For example, CD271+ uveal melanoma stem cells may undergo vasculogenic mimicry in 3D Matrigel culture (78). Another previous study revealed that nicastrin, a novel typeⅠtransmembrane glycoprotein, is associated with breast cancer stem cell properties using Matrigel culture (79).…”

Cancer stem cells and their vascular niche: Do they benefit from each other?

“…Vascular-like channels formed by CSC-derived endothelial-like cells or mural cells were described as vasculogenic mimicry (VM) [16,40,77,80,[83][84][85][86]. VM refers to the vascular-like structure formed by aggressive tumor cells by mimicking the pattern of embryonic vasculogenic networks [39].…”