Mechanism of tumour vascularization in experimental lung metastases

Vanessza Szabo, Edina Bugyik, Katalin Dezso, Nora Ecker, Peter Nagy, Jozsef Timar, Jozsef Tovari, Viktoria Laszlo, Victoria L. Bridgeman, Elaine Wan, Sophia Frentzas, Peter B. Vermeulen, Andrew R. Reynolds, Balazs Dome, Sandor Paku

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)384-396
Number of pages13
JournalJournal of Pathology
Volume235
Issue number3
DOIs
Publication statusPublished - Feb 1 2015

Keywords

  • Angiogenesis
  • Arterialization
  • Lung metastasis
  • Vessel co-option

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Mechanism of tumour vascularization in experimental lung metastases'. Together they form a unique fingerprint.

  • Cite this

    Szabo, V., Bugyik, E., Dezso, K., Ecker, N., Nagy, P., Timar, J., Tovari, J., Laszlo, V., Bridgeman, V. L., Wan, E., Frentzas, S., Vermeulen, P. B., Reynolds, A. R., Dome, B., & Paku, S. (2015). Mechanism of tumour vascularization in experimental lung metastases. Journal of Pathology, 235(3), 384-396. https://doi.org/10.1002/path.4464