An Update on Molecular Pathways Regulating Vasculogenic Mimicry in Human Osteosarcoma and Their Role in Canine Oncology

Abstract

Canine tumors are valuable comparative models for human counterparts, especially to explore novel biomarkers and to understand pathways and processes involved in metastasis. Vasculogenic mimicry (VM) is a unique property of malignant cancer cells which promote metastasis. Thus, it represents an opportunity to investigate both the molecular mechanisms and the therapeutic targets of a crucial phenotypic malignant switch. Although this biological process has been largely investigated in different human cancer types, including osteosarcoma, it is still largely unknown in veterinary pathology, where it has been mainly explored in canine mammary tumors. The presence of VM in human osteosarcoma is associated with poor clinical outcome, reduced patient survival, and increased risk of metastasis and it shares the main pathways involved in other type of human tumors. This review illustrates the main findings concerning the VM process in human osteosarcoma, search for the related current knowledge in canine pathology and oncology, and potential involvement of multiple pathways in VM formation, in order to provide a basis for future investigations on VM in canine tumors.

Keywords: comparative oncology; dog; molecular pathways; osteosarcoma; vasculogenic mimicry.

Figure 1

Schematic representation of VM through cancer cells (in purple) forming a vessel containing red blood cells. Figure shows the main molecular pathways involved in the VM process in human osteosarcoma highlighting, in underlined bold, those found to be related with VM presence or tubular/vessel-like formation in vitro in dog.

Figure 2

Localization of the principal molecular pathways involved in VM. Figure shows the cellular and tumor microenvironmental distribution of the human OSA pathways resumed in the review showing, when known, the possible interactions (black arrow) between them. Multiple arrows show multiple interactions between pathways.