Papillary carcinoma of the thyroid: low expression of NCAM (CD56) is associated with downregulation of VEGF‐D production by tumour cells
- 15 June 2007
- journal article
- research article
- Published by Wiley in The Journal of Pathology
- Vol. 212 (4), 411-419
- https://doi.org/10.1002/path.2183
Abstract
The expression of NCAM was investigated in tissue sections of 61 cases of papillary carcinoma and in 14 lymph node metastases using immunohistochemistry. Tumour cells of 18 primary tumours were not stained, whereas in the remaining 43 cases, NCAM was expressed in less than 5% tumour cells. Similar results were obtained when NCAM expression was evaluated at the RNA level. Reduced expression of NCAM is an early event since 6/15 cases (40%) of micro-carcinoma were NCAM-negative. NCAM-positive tumour cells were more often located at the invasion front of the tumour. It has been reported that NCAM expression may affect lymphangiogenesis. In tissue sections immunostained for podoplanin, it was found that lymphatic vessels were extremely rare inside the body of the tumour, and were mostly associated with foci of chronic inflammation and/or of reparative fibrosis. Lymphangiogenesis is sustained by VEGF-C, VEGF-D, and FGF2. Analysis of micro-dissected samples of the tumour and of the paired normal thyroid tissue revealed that RNA transcripts for VEGF-D were significantly less numerous in the tumour tissue (p = 0.001). The potential role of NCAM in tumour cell biology was investigated by silencing the NCAM gene in the TPC1 thyroid papillary carcinoma cell line. It was found that NCAM down-regulation caused a significant reduction (p < 0.05) in the expression of both VEGF-C and VEGF-D mRNAs. In addition, NCAM-silenced TPC-1 cells were more adhesive to different extracellular matrix components, and were less efficient in cell migration (59% reduction; p < 0.05) and invasiveness (68% reduction). These latter results confirm that modifications of NCAM expression cause profound alterations in the adhesive and migratory properties of tumour cells, but are in apparent discrepancy with the observation that loss of NCAM is usually associated with increased tumour invasiveness in vivo. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.This publication has 19 references indexed in Scilit:
- VEGF-D expression and lymph vessels play an important role for lymph node metastasis in papillary thyroid carcinomaLaboratory Investigation, 2005
- Lymph vessel density correlates with nodal status, VEGF-C expression, and prognosis in breast cancerBreast Cancer Research and Treatment, 2005
- Molecular and cellular mechanisms of lymphangiogenesisEuropean Journal of Surgical Oncology, 2005
- Loss of Neural Cell Adhesion Molecule Induces Tumor Metastasis by Up-regulating LymphangiogenesisCancer Research, 2004
- Molecular regulation of the VEGF family – inducers of angiogenesis and lymphangiogenesisAPMIS, 2004
- Lymphangiogenesis in tumors: What do we know?Microscopy Research and Technique, 2003
- Cellular signalling mechanisms of neural cell adhesion molecules Anitha K Panicker Mona BuhusiFrontiers in Bioscience-Landmark, 2003
- Alternative mRNA splicing in colon cancer causes loss of expression of neural cell adhesion moleculeSurgery, 2001
- N-CAM modulates tumour-cell adhesion to matrix by inducing FGF-receptor signallingNature, 2001
- Cellular signaling by neural cell adhesion molecules of the immunoglobulin superfamilyDevelopmental Dynamics, 2000