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Semaphorin 3E expression correlates inversely with Plexin D1 during tumor progression
Ilse Roodink1, Gürsah Kats, Léon van Kempen
1Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. I.Roodink@pathol.umcn.nl
The American Journal of Pathology
|November 1, 2008
Summary
Plexin D1 (PLXND1) expression correlates with melanoma invasion and metastasis. However, semaphorin 3E (Sema3E) surprisingly inhibits tumor spread, suggesting it is not the activating ligand for PLXND1 in melanoma progression.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Plexin D1 (PLXND1) is found on tumor cells and vessels in various human cancers.
- The role of PLXND1 in tumor development is not well understood.
- Semaphorin 3E (Sema3E), a PLXND1 ligand, has been linked to cancer invasion and metastasis.
Purpose of the Study:
- To investigate Plexin D1 (PLXND1) and Semaphorin 3E (Sema3E) expression during melanoma progression.
- To determine the functional role of the PLXND1-Sema3E interaction in melanoma development.
Main Methods:
- Analysis of PLXND1 and Sema3E expression in naevi, in situ melanomas, and metastatic melanomas.
- Assessment of invasion levels using Clark's criteria.
- Overexpression of Sema3E in a xenograft model of metastatic melanoma.
Main Results:
- PLXND1 expression increased with melanoma invasion depth.
- 89% of metastatic melanomas showed PLXND1 staining on tumor cells.
- Sema3E expression was inversely correlated with tumor progression and decreased metastatic potential when overexpressed.
Conclusions:
- PLXND1 expression is strongly associated with melanoma invasiveness and metastasis.
- Sema3E acts as an inhibitor of melanoma metastasis, suggesting it is not the activating ligand for PLXND1 in this context.
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