Endothelial cell expression patterns

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/12 (2006.01) A61K 31/7088 (2006.01) A61K 35/12 (2006.01) A61K 38/17 (2006.01) A61K 39/395 (2006.01) A61K 48/00 (2006.01) A61K 49/00 (2006.01) A61K 51/10 (2006.01) A61P 35/00 (2006.01) C07K 14/705 (2006.01) C07K 14/82 (2006.01) C07K 16/18 (2006.01) C07K 16/30 (2006.01) C12Q 1/02 (2006.01) C12Q 1/68 (2006.01) G01N 33/566 (2006.01) G01N 33/574 (2006.01)

Patent

CA 2443995

To gain a better understanding of tumor angiogenesis, new techniques for isolating endothelial cells (ECs) and evaluating gene expression patterns were developed. When transcripts from ECs derived from normal and malignant colorectal tissues were compared with transcripts from non-endothelial cells, over 170 genes predominantly expressed in the endothelium were identified. Comparison between normal- and tumor-derived endothelium revealed 79 differentially expressed genes, including 46 that were specifically elevated in tumor-associated endothelium. Experiments with representative genes from this group demonstrated that most were similarly expressed in the endothelium of primary lung, breast, brain, and pancreatic cancers as well as in metastatic lesions of the liver. These results demonstrate that neoplastic and normal endothelium in humans are distinct at the molecular level, and have significant implications for the development of anti-angiogenic therapies in the future.

Afin de mieux comprendre l'angiogenèse des tumeurs, on a mis au point de nouvelles techniques pour isoler les cellules endothéliales (EC) et évaluer les motifs d'expression des gènes. Lorsque l'on a comparé les transcrits provenant des EC dérivés des tissus colorectaux normaux et malins aux transcrits provenant des cellules non endothéliales, on a identifié plus de 170 gènes exprimés de façon prédominante dans l'endothélium. La comparaison entre l'endothélium normal et celui dérivé des tumeurs a montré 79 gènes exprimés de façon différentielle, y compris 46 qui ont été spécifiquement élevés dans l'endothélium associé à la tumeur. Des expériences avec des gènes représentatifs de ce groupe ont montré que la plupart ont été exprimés de façon similaire dans l'endothélium du cancer primaire du poumon, du sein, du cerveau ainsi que dans des lésions métastasiques du foie. Les résultats ont montré que chez les humains l'endothélium néoplasique et celui normal se distinguent au niveau moléculaire, ce qui peut avoir une influence importante sur le développement des thérapies anti-angiogéniques de l'avenir.

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