Abstract 5158: Plastic tumor cells engaged in vasculogenic mimicry produce PDGF-B and attract structural support

Abstract

Abstract In developmental angiogenesis, pericytes are recruited by PDGF-B-expressing endothelial cells to remodel, stabilize and support the immature blood vessel. In a process called vasculogenic mimicry (VM) highly aggressive tumor cells gain the unique ability to dedifferentiate into multiple cellular phenotypes, and obtain endothelial-like characteristics. This process can lead to the formation of vasculogenic-like matrix-embedded networks, i.e. vascular-like structures, contributing to circulation. The presence of VM is associated with increased tumor malignancy. Interestingly, also the expression of PDGF in tumor cells has been demonstrated to be associated with an increased grade of malignancy. As plastic, highly aggressive tumor cells form vasculogenic-like structures resembling immature vessels, we hypothesize that plastic tumor cells engaged in VM also functionally resemble endothelial cells by seeking structural support. We demonstrate that plastic, aggressive melanoma cells transcribe and secrete PDGF-B, while in poorly aggressive melanoma cells, PDGF-B is absent. Myofibroblasts, acquired from the human vena saphena, cultured in the presence of plastic tumor cell conditioned medium display an activated phenotype. Additionally, in vitro analysis of 3D-culture on Matrigel demonstrated the functional contribution of myofibroblasts to plastic tumor cells as they structurally support the VM-characteristic networks formed. Immunohistochemical analysis of a series of cutaneous melanoma tissues showed a gradient PDGF-B staining towards the outer surface of the nest structures, i.e. the tumor cells aligning the VM-characteristic matrix networks. Consistent with the above described data, we observed staining for alpha-smooth muscle actin (α-SMA), a pericyte-specific marker, within the VM-characteristic matrix networks, thereby revealing the presence of pericytes inside these networks. Together our results demonstrate that highly aggressive, VM-positive tumor cells do not solely resemble endothelial cells phenotypically, but also actively behave like endothelial cells by producing PDGF-B and attracting structural support to their immature structures. The current findings suggest that targeting of pericytes may have an unexpected anti-tumor activity through affecting vasculogenic mimicry. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5158. doi:10.1158/1538-7445.AM2011-5158