Fact or Fiction, It Is Time for a Verdict on Vasculogenic Mimicry?

Abstract

The term vasculogenic mimicry (VM) refers to the capacity of certain cancer cells to form fluid-conducting structures within a tumor in an endothelial cell (EC)-free manner. Ever since its first report by Maniotis in 1999, the existence of VM has been an extremely contentious issue. The overwhelming consensus of the literature suggests that VM is frequently observed in highly aggressive tumors and correlates to lower patient survival. While the presence of VM in vivo in animal and patient tumors are claimed upon the strong positive staining for glycoproteins (Periodic Acid Schiff, PAS), it is by no means universally accepted. More controversial still is the existence of an in vitro model of VM that principally divides the scientific community. Original reports demonstrated that channels or tubes occur in cancer cell monolayers in vitro when cultured in matrigel and that these structures may support fluid movement. However, several years later many papers emerged stating that connections formed between cancer cells grown on matrigel represented VM. We speculate that this became accepted by the cancer research community and now the vast majority of the scientific literature reports both presence and mechanisms of VM based on intercellular connections, not the presence of fluid conducting tubes. In this opinion paper, we call upon evidence from an exhaustive review of the literature and original data to argue that the majority of in vitro studies presented as VM do not correspond to this phenomenon. Furthermore, we raise doubts on the validity of concluding the presence of VM in patient samples and animal models based solely on the presence of PAS+ staining. We outline the requirement for new biomarkers of VM and present criteria by which VM should be defined in vitro and in vivo .

Vasculogenic Mimicry: A Promising Prognosticator in Head and Neck Squamous Cell Carcinoma and Esophageal Cancer? A Systematic Review and Meta-Analysis

“…Vasculogenic mimicry (VM) was first introduced in 1999 to indicate a remarkable feature of aggressive melanoma cells to generate vessel-like, blood-containing channels which facilitate tumor perfusion regardless of surrounding endothelial blood vessels [11,12]. Clinically, VM is commonly assessed in patient samples by immunohistochemical (IHC) analysis of periodic acid-Schiff (PAS) positive, and CD31 or CD34 negative vessel-like structures [13].…”

The Osteosarcoma Microenvironment: A Complex but Targetable Ecosystem

“…Human OS cell lines (U2OS [106], MG-63 [105]) and aggressive canine cell lines [107] are able to form vessel-like structures in three-dimensional cultures. Vascular mimicry mechanisms remain largely unknown, often being assessed via inappropriate and biased in vitro assays [108]. Nevertheless, a subpopulation of OS tumor cells co-expressing high levels of both VEGF and its receptor VEGFR-1 has been described as an important factor of aggressiveness [109].…”

SOX7 blocks vasculogenic mimicry in oral squamous cell carcinoma

“…Identi cation of vasculogenic mimicry CD31/PAS double staining was evaluated blindly by two oral pathologists (KYO and SDH). Based on recent reviews of VM [22,23], VM + was de ned as the presence of CD31 − /PAS + vessel-like structures surrounded by tumor cells on the non-luminal side. Although red blood cells may be observed in the lumen, the absence of endothelial cells was con rmed by the absence of CD31 expression on the luminal side.…”