title: Laminin alpha2 chain-positive vessels and epidermal growth factor in lung neuroendocrine carcinoma: a model of a novel cooperative role of laminin-2 and epidermal growth factor in vessel neoplastic invasion and metastasis.
abstract: Capillaries expressing the laminin alpha2 chain in basement membranes may be considered early developing vessels in normal and neoplastic human tissues. Therefore, we investigated whether up-regulation of this extracellular matrix protein favors transendothelial migration of neoplastic cells and then metastasis. In lung small and large cell neuroendocrine carcinomas, which exhibit a stronger metastatic tendency among carcinomas, laminin alpha2 chain-positive vessels were more numerous than in carcinoid tumors and supraglottis, breast, and lung non-small cell carcinomas, suggesting a direct relationship between these vessels and metastasis. In vitro studies showed that epidermal growth factor (EGF) induced a more efficient migration of the AE-2 lung neuroendocrine carcinoma cell line through the purified laminin alpha2 chain rather than through the laminin beta1 chain and fibronectin. AE-2 cells constitutively expressed all EGF receptors and the alpha6beta1 integrin, which is one of the laminin alpha2 chain receptors. EGF up-regulated alpha6beta1 expression in several tumors. In this regard, we show that EGF increased the chemo-kinetic migration of AE-2 cells through EAHY endothelial monolayers, which was inhibited by the anti-alpha6 integrin chain monoclonal antibody. These data indicate that laminin alpha2 chain and alpha6beta1 may be mutually involved in EGF-dependent migration of AE-2 cells and that laminin alpha2 chain-positive vessels may favor metastasis of EGF-dependent tumors.
authors.affiliation: Department of Experimental Medicine and Pathology, University of Rome La Sapienza, Rome, Italy. domenico.vitolo@uniroma1.it
authors.forename: Domenico
authors.initials: D
authors.lastname: Vitolo
authors.forename: Luciano
authors.initials: L
authors.lastname: Ciocci
authors.forename: Gloria
authors.initials: G
authors.lastname: Deriu
authors.forename: Silvia
authors.initials: S
authors.lastname: Spinelli
authors.forename: Stefania
authors.initials: S
authors.lastname: Cortese
authors.forename: Laura
authors.initials: L
authors.lastname: Masuelli
authors.forename: Stefania
authors.initials: S
authors.lastname: Morrone
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Filice
authors.forename: Giorgio Furio
authors.initials: GF
authors.lastname: Coloni
authors.forename: Pier Giorgio
authors.initials: PG
authors.lastname: Natali
authors.forename: Carlo Davide
authors.initials: CD
authors.lastname: Baroni
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002196:Capillaries / Q000737:chemistry; D002276:Carcinoid Tumor / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D018278:Carcinoma, Neuroendocrine / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007797:Laminin / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D007797:Laminin; C102645:laminin alpha 2; D004815:Epidermal Growth Factor