Loss of neural cell adhesion molecule induces tumor metastasis by up-regulating lymphangiogenesis

Reduced expression of neural cell adhesion molecule (NCAM) has been implicated in the progression to tumor malignancy in cancer patients. Previously, we have shown that the loss of NCAM function causes the formation of lymph node metastasis in a transgenic mouse model of pancreatic beta cell carcino...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2004-12, Vol.64 (23), p.8630-8638
Main Authors: CRNIC, Ivana, STRITTMATTER, Karin, CAVALLARO, Ugo, KOPFSTEIN, Lucie, JUSSILA, Lotta, ALITALO, Kari, CHRISTOFORI, Gerhard
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Biological and medical sciences
Islets of Langerhans - pathology
Lymphangiogenesis - physiology
Lymphatic Metastasis
Lymphatic Vessels - metabolism
Lymphatic Vessels - pathology
Medical sciences
Mice
Mice, Transgenic
Neovascularization, Pathologic - pathology
Neural Cell Adhesion Molecules - biosynthesis
Neural Cell Adhesion Molecules - deficiency
Pancreatic Neoplasms - blood supply
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
Pharmacology. Drug treatments
Up-Regulation
Vascular Endothelial Growth Factor C - biosynthesis
Vascular Endothelial Growth Factor D - biosynthesis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Reduced expression of neural cell adhesion molecule (NCAM) has been implicated in the progression to tumor malignancy in cancer patients. Previously, we have shown that the loss of NCAM function causes the formation of lymph node metastasis in a transgenic mouse model of pancreatic beta cell carcinogenesis (Rip1Tag2). Here we show that tumors of NCAM-deficient Rip1Tag2 transgenic mice exhibit up-regulated expression of the lymphangiogenic factors vascular endothelial growth factor (VEGF)-C and -D (17% in wild-type versus 60% in NCAM-deficient Rip1Tag2 mice) and, with it, increased lymphangiogenesis (0% in wild-type versus 19% in NCAM-deficient Rip1Tag2 mice). Repression of VEGF-C and -D function by adenoviral expression of a soluble form of their cognate receptor, VEGF receptor-3, results in reduced tumor lymphangiogenesis (56% versus 28% in control versus treated mice) and lymph node metastasis (36% versus 8% in control versus treated mice). The results indicate that the loss of NCAM function causes lymph node metastasis via VEGF-C- and VEGF-D-mediated lymphangiogenesis. These results also establish Rip1Tag2;NCAM-deficient mice as a unique model for stochastic, endogenous tumor lymphangiogenesis and lymph node metastasis in immunocompetent mice.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-04-2523