Lung cancer neovascularisation: Cellular and molecular interaction between endothelial and lung cancer cells

Background: Novel vascular-independent conduits have been observed in some cancers. These have been variously described as vasculogenic mimicry, mosaic vessel formation, vascular co-option and intra-tumour embryonic-like vasculogenesis. Despite lung cancer being the most common cancer worldwide, there is little information on its neovascularisation or the pathways involved. Methods: An in vitro model involving co-cultures of microvascular lung endothelial cells and squamous or adenocarcinoma lung cancer cells was developed to assess their angiogenic interaction. Cells were incubated and examined by phase contrast microscopy and by immunocytochemistry in both mono- and co-cultures. Cultured cells and lung cancer tissue sections were assessed for new tumour vessel formation, expression of the endothelial marker CD31 and morphology. Results: Lung tumour cells and endothelial cells interacted morphologically via pseudopodia and used alternative pathways to generate new vessels. Co-culturing microvascular endothelial and squamous carcinoma cells led to endothelial cells surrounding tumour cells and the tumour cells being incorporated into vessel walls. Co-culturing endothelial and adenocarcinoma cells resulted in cellular contact and the formation of tumour cell bridges around clusters of endothelial cells. These adencocarcinoma cells became strongly positive for CD31. Tumour tissue section studies supported the in vitro findings. Conclusion: Lung carcinoma cells when co-cultured with lung endothelial cells modify their cellular and molecular features that encourage alternative means of providing blood supply. The mechanisms under-pinning these non-angiogenic processes need to be further investigated and should be considered when anti-tumour therapeutic interventions are being considered. (C) 2013 Elsevier GmbH. All rights reserved.