[Mechanism of tumour vascularisation in experimental lung metastases]

Treatment of patients with lung metastases remains a major challenge. A possible target for therapies is the inhibition of vascularization of metastases. We examined the vascularisation process of lung metastasis in six different preclinical models and found that the tumours incorporated the pre-existing alveolar capillaries (i.e. vessel co-option). During the initial phase of vessel co-option, the incorporated capillaries were still sheathed by pneumocytes, but these incorporated vessels subsequently underwent different fates dependent on the model. In five of the models examined (B16, HT1080, HT25, C26 and MAT-B-III), the tumour cells gradually stripped the pneumocytes from the vessels. These dissected pneumocytes underwent fragmentation, but the incorporated microvessels survived. In the sixth model (C38), the tumour cells failed to invade the alveolar walls. Instead, they induced the development of vascularised desmoplastic tissue columns. In conclusion, our data show that lung metastases can vascularise by co-opting the pulmonary microvasculature.