Accession Number : ADA588423


Title :   Fibroblast Activation Protein-Alpha, a Serine Protease that Facilitates Metastasis by Modification of Diverse Microenvironments


Descriptive Note : Revised final rept. 2 Sep 2008-1 Sep 2011


Corporate Author : ARKANSAS UNIV AT LITTLE ROCK


Personal Author(s) : Kelly, Jr, Thomas J ; Simms, Avis E ; Huang, Yan ; Mazur, Anna


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a588423.pdf


Report Date : Oct 2011


Pagination or Media Count : 123


Abstract : Our overarching hypothesis is that FAP functions with other proteases in an extracellular communication network to digest certain proteins, thereby exposing signals stored in peptide regions that enable breast cancer cells to thrive in diverse microenvironments. FAP likely has important functions in two parts of the metastatic cascade: 1) FAP and proteases such as MMP-1 and MMP-9 cooperate to produce fragments of ECM proteins during adjacent tissue remodeling and these derivative peptides promote fibroblast growth, ECM deposition and angiogenesis; 2) cancer cell membrane FAP cleaves precursive A2AP to generate the more effective derivative for protecting and stabilizing fibrin within ECM margins of the expanding neoplastic cell mass as well as fibrin within cancer cell/fibrin/platelet emboli that lead to hematogenous metastasis. We believe that peptides that target and inhibit FAP on FAP-expressing cells can be produced by taking advantage of the substrate/active-site binding specificity of FAP.


Descriptors :   *BREAST CANCER , *FIBROBLASTS , *METASTASIS , *SERINE , CELLS(BIOLOGY) , COMMUNICATIONS NETWORKS , DEPOSITION , ELECTRONIC COUNTERMEASURES , FIBRIN , MEMBRANES(BIOLOGY) , PROTEINS


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE