The Role of Dipeptidyl Peptidase IV in Lung Metastasis of Breast Cancer Cells
Annual rept. 1 May 1998-30 Apr 2000
CORNELL UNIV ITHACA NY
Pagination or Media Count:
Our studies focused on 1 cloning and sequencing of wild-type endothelial DPP IV wtDPP IV and preparation of truncated DPP IV tDPP IV 2 identification of surface-associated fibronectin polymers polyFN as DPP IV ligand 3 use of DPP IV Fischer 344CRJ rats as protein-knock-outs in metastasis and 4 identification of the DPP IVFN binding domains. A lull-length clone of endothelial wtDPP IV was isolated from a rat lung cDNA library that was identical to hepatic DPP IV. Acid extraction of rat lung yielded a tDPP IV, which was an effective inhibitor of breast cancer cell adhesion to wtDPP IV and lung metastasis. The DPP IV ligand, polyFN, provides multiple binding sites for DPP IV, thereby allowing lung vascular arrest of cancer cells under hemodynamic conditions. Fischer 344CRJ rats are unsuitable as DPP IV protein knock-out model, because lung endothelia leak expression of DPP IV and are able to support breast cancer cell arrest. The DPP IV binding domains of FN was localized to an N- terminal 30-kDa region and FN type III repeats 13 to 14. Three approximately equal size fragments of the extracellular domain of DPP IV were expressed as GST fusion proteins and are currently studied for FN binding.
- Anatomy and Physiology
- Medicine and Medical Research