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

Am J Pathol. 2006 Mar;168(3):991-1003. doi: 10.2353/ajpath.2006.041310.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Capillaries / chemistry
  • Carcinoid Tumor / blood supply
  • Carcinoid Tumor / metabolism
  • Carcinoid Tumor / pathology
  • Carcinoma, Neuroendocrine / blood supply
  • Carcinoma, Neuroendocrine / metabolism
  • Carcinoma, Neuroendocrine / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Epidermal Growth Factor / genetics
  • Epidermal Growth Factor / metabolism*
  • Gene Expression
  • Humans
  • Laminin / analysis
  • Laminin / antagonists & inhibitors
  • Laminin / metabolism*
  • Lung Neoplasms / blood supply
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Models, Biological
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Up-Regulation


  • Antibodies, Monoclonal
  • Laminin
  • laminin alpha 2
  • Epidermal Growth Factor