Vascular phenotype in angiogenic and non-angiogenic lung non-small cell carcinomas

Abstract

We have previously described a group of non-small cell lung carcinomas without morphological evidence of neo-angiogenesis. In these tumours neoplastic cells fill up the alveoli and the only vessels present appear to belong to the trapped alveolar septa. In the present study we have characterised the phenotype of the vessels present in these non-angiogenic tumours, in normal lung and in angiogenic non-small cell lung carcinomas. The vessels, identified by the expression of CD31, were scored as mature when expressing the epitope LH39 in the basal membrane and as newly formed when expressing aVb3 on the endothelial cells and/or lacking LH39 expression. In the nine putative non-angiogenic cases examined, the vascular phenotype of all the vessels was the same as that of alveolar vessels in normal lung: LH39 positive and aVb3 variable or negative. Instead in 104 angiogenic tumours examined, only a minority of vessels (mean 13.1%; range 0-60%) expressed LH39, while aVb3 (in 45 cases) was strongly expressed on many vessels (mean 55.5%; range 5-90%). We conclude that in putative non-angiogenic tumours the vascular phenotype is that of normal vessels and there is no neo-angiogenesis. This type of cancer may be resistant to some anti-angiogenic therapy and different strategies need to be developed.

Vascular patterns in reactive lymphoid tissue and in non-Hodgkin's lymphoma

“…The first marker was the expression of the LH39 epitope interacting with the antibody LH39, which is expressed on the basal membrane of capillaries and small venules in a variety of normal human tissues but is absent in small vessels present in pyogenic granulomas or nonspecific oral ulceration (Almeida et al, 1992a, b). These data have suggested that the detection of LH39 staining discriminates between mature and immature vessels, as supported by four further studies on oral carcinomas (Almeida et al, 1992a), breast carcinomas (Kakolyris et al, 1999) and lung cancer (Kakolyris et al, 1999;Passalidou et al, 2002).…”

“…Furthermore, the balance between neoangiogenesis and vascular regression, still maintained in neoplastic follicles, is lost in diffuse large cell lymphomas. Large B-cell lymphomas therefore have a vascular (Kakolyris et al, 1999(Kakolyris et al, , 2000Passalidou et al, 2002).…”

“…Many authors have reported, on brain, skin, kidney and lung, that endothelial cells express it to varying degrees (Rabb et al, 1996;Navratil et al, 1997;Pazouki et al, 1997;Passalidou et al, 2002) although in one study of normal human breast tissue the endothelium was negative for aVb3 (Gasparini et al, 1998). While it is well established that endothelial expression of aVb3 is essential for angiogenesis induced by basic fibroblastic growth factor or tumour necrosis factor (Brooks et al, 1994;Friedlander et al, 1995), it has also been found that it can be upregulated in resting endothelium by a variety of biological stimuli (Tang et al, 1994) and that it is also present on resting endothelial cells (Conforti et al, 1992).…”

Micronodular transformation as a novel mechanism of VEGF-A-induced metastasis

“…Interestingly, treated tumors still presented with a nodular phenotype, but the nodules lacked These results suggest that metastatic emboli escape the tumor during early stages of tumor growth. Furthermore, they show that ZD6474 treatment does not inhibit metastatic outgrowth in lungs, possibly reflecting the potential to grow by cooption in highly vascularized tissues (Passalidou et al, 2002;Leenders et al, 2004). Furthermore, the intravascular localization of these metastases, very near to air-filled alveoli, may enable tumor growth without additional angiogenesis.…”

“…First, clinical and animal data show that for metastatic tumors in brains, lungs or livers, induction of angiogenesis is not a prerequisite as for these tumors the preexistent vascular bed may allow tumor growth (Pezzella et al, 1997;Al-Mehdi et al, 2000;Neves et al, 2001;Vermeulen et al, 2001;Kim et al, 2002;Kusters et al, 2002;Passalidou et al, 2002;Auguste et al, 2005). Secondly, recent reports demonstrated the presence of intravascular endothelium-covered tumor cell clusters in the primary tumor as origin of metastasis (Sugino et al, 1993(Sugino et al, , 2002(Sugino et al, , 2004.…”