Laminin alpha2 chain (merosin M chain) distribution and VEGF, FGF(2), and TGFbeta1 gene expression in angiogenesis of supraglottic, lung, and breast carcinomas.
The prognostic significance of vessel quantification in human solid tumours is still debated, due to the presence of multiple factors modulating neoangiogenesis and the invasiveness of neoplastic cells. This study examined ten supraglottic squamous carcinomas, ten non-small cell lung carcinomas (three squamous, five bronchioloalveolar, two adenocarcinomas), and nine classic (NOS) invasive ductal breast carcinomas. The properties studied in these tumours were vascularity; the immunohistochemical distribution of adhesion molecules such as alpha2beta1, alpha3beta1, alpha4beta1, alpha5beta1, alpha6beta4, and ICAM-1 in endothelial cells; extracellular matrix proteins (ECMPs) and laminin alpha2 chain (merosin M chain) in basal membranes of vessels; and gene expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF2), and transforming growth factor beta1 (TGFbeta1), by in situ hybridization. Independently of tumour type and vascularity, laminin alpha2 chain expression was observed in the basal membranes of a limited proportion of vessels. In vitro experiments demonstrated laminin alpha2 chain expression mainly in early endothelial cell cultures, suggesting that laminin alpha2 chain expression in vivo can be considered a marker of early angiogenesis. Stromal and parenchymal vascularity was associated with laminin alpha2 chain expression in supraglottic carcinomas, whereas in the other tumours, laminin alpha2 chain-positive vessels were observed only in the stroma. In supraglottic carcinomas, VEGF-positive cells were mainly represented by neoplastic cells, whereas in the other tumours, the great majority of VEGF-positive cells were macrophages and fibroblasts. FGF2- and TGFbeta1-positive cells were macrophages and fibroblasts in all tumours. These observations suggest that in addition to the quantification and distribution of vessels, evaluation of their maturation may contribute to a better understanding of the role of angiogenesis in the growth and spread potential of solid tumours. In this regard, in supraglottic carcinomas, parenchymal angiogenesis seems to be regulated mainly by neoplastic cells, which may help to explain their high metastatic potential; in solid tumours of different histogenesis, different cells might be responsible for modulating tumour angiogenesis.
Vitolo
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Department of Experimental Medicine and Pathology, University La Sapienza, Roma, Italy.
Ciocci
L
L
Cicerone
E
E
Rossi
C
C
Tiboni
F
F
Ferrauti
P
P
Gallo
A
A
Baroni
C D
CD
D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000098:blood supply / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000098:blood supply / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000378:metabolism; D005260:Female; D005931:Glottis; D006801:Humans; D007797:Laminin / Q000378:metabolism*; D007822:Laryngeal Neoplasms / Q000098:blood supply / Q000378:metabolism; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009369:Neoplasms / Q000098:blood supply* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D043925:Angiogenesis Inducing Agents; D014408:Biomarkers, Tumor; D007797:Laminin; D009363:Neoplasm Proteins; C102645:laminin alpha 2