Mechanism of tumour vascularization in experimental lung metastases.

The appearance of lung metastases is associated with poor outcome and the management of patients with secondary pulmonary tumours remains a clinical challenge. We examined the vascularization process of lung metastasis in six different preclinical models and found that the tumours incorporated the pre-existing alveolar capillaries (ie 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 vascularized desmoplastic tissue columns. Finally, we examined the process of arterialization in lung metastases and found that they became arterialized when their diameter grew to exceed 5 mm. In conclusion, our data show that lung metastases can vascularize by co-opting the pulmonary microvasculature. This is likely to have important clinical implications, especially with respect to anti-angiogenic therapies.

[Hereditary cancer predisposition syndromes associated with sarcomas]. / Felnottkori szarkómához asszociált örökletes daganatszindrómák.

Based on our current knowledge, 5-10% of all malignancies are part of hereditary cancer syndromes. Although the increasing diagnostic role of molecular genetic testing makes us able to recognize more hereditary cancer patients, the careful exploration of family and clinical history by physicians is still the most important step for the diagnosis. In our review we deal with mesenchymal tumours associated with hereditary syndromes. Sarcomas comprise only 1% of all malignancies, but they often associate with familiar diseases so they can serve as an indicator of these syndromes. The diagnosis of hereditary cancer predisposition syndromes is essential to ensure appropriate therapy and follow-up for our patients.

Mechanisms of vascularization in murine models of primary and metastatic tumor growth.

Directed capillary ingrowth has long been considered synonymous with tumor vascularization. However, the vasculature of primary tumors and metastases is not necessarily formed by endothelial cell sprouting; instead, malignant tumors can acquire blood vessels via alternative vascularization mechanisms, such as intussusceptive microvascular growth, vessel co-option, and glomeruloid angiogenesis. Importantly, in response to anti-angiogenic therapies, malignant tumors can switch from one vascularization mechanism to another. In this article, we briefly review the biological features of these mechanisms and discuss on their significance in medical oncology.