Evidence |
First, we examined the production of the three VEGF homologs. VEGFA was expressed at higher levels in the neuroendocrine tumor cells and the immune cells of the primary tumor compared to the metastatic tumor (Fig. 2C). VEGFA is known to be expressed by tumor-associated macrophages (TAMs), and the differential expression may indicate a lower influx of TAMs at the metastatic site (Ugel et al. 2015). VEGFB was expressed at high levels in the fibroblasts of the primary tumor but not in its metastatic counterparts and TGFB1, whereas VEGFC was expressed at comparable levels in Endothelial cellss (Fig. 2D). In contrast, the metastatic Endothelial cellss expressed higher levels of the VEGF receptor gene FLT1 and significantly higher levels of KDR, the latter being the primary VEGF receptor for mitogenic signaling (Fig. 2D). Additionally, the metastatic Endothelial cellss produced PDGFB, which the primary tumor Endothelial cellss did not, establishing a possible paracrine signaling support for the metastatic PDGFRB-expressing pericytes (Fig. 2D). |