title: Mechanism of tumour vascularization in experimental lung metastases.
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.
authors.affiliation: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
authors.forename: Vanessza
authors.initials: V
authors.lastname: Szabo
authors.forename: Edina
authors.initials: E
authors.lastname: Bugyik
authors.forename: Katalin
authors.initials: K
authors.lastname: Dezso
authors.forename: Nora
authors.initials: N
authors.lastname: Ecker
authors.forename: Peter
authors.initials: P
authors.lastname: Nagy
authors.forename: Jozsef
authors.initials: J
authors.lastname: Timar
authors.forename: Jozsef
authors.initials: J
authors.lastname: Tovari
authors.forename: Viktoria
authors.initials: V
authors.lastname: Laszlo
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Bridgeman
authors.forename: Elaine
authors.initials: E
authors.lastname: Wan
authors.forename: Sophia
authors.initials: S
authors.lastname: Frentzas
authors.forename: Peter B
authors.initials: PB
authors.lastname: Vermeulen
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Reynolds
authors.forename: Balazs
authors.initials: B
authors.lastname: Dome
authors.forename: Sandor
authors.initials: S
authors.lastname: Paku
mesh_terms: D056809:Alveolar Epithelial Cells / Q000473:pathology; D000818:Animals; D001808:Blood Vessels / Q000473:pathology / Q000503:physiopathology*; D001980:Bronchi / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005354:Fibrosarcoma / Q000473:pathology; D006801:Humans; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000098:blood supply* / Q000503:physiopathology / Q000556:secondary*; D015674:Mammary Neoplasms, Animal / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000503:physiopathology*; D051381:Rats
keywords: angiogenesis; arterialization; lung metastasis; vessel co-option