Accession Number : ADA535000


Title :   Evaluation of Fibroblast Activation Protein-Alpha (FAP) as a Diagnostic Marker and Therapeutic Target in Prostate Cancer


Descriptive Note : Annual summary 1 Dec 2006-30 Nov 2009


Corporate Author : JOHNS HOPKINS UNIV BALTIMORE MD SCHOOL OF MEDICINE


Personal Author(s) : Brennen, Nathaniel


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a535000.pdf


Report Date : Dec 2009


Pagination or Media Count : 43


Abstract : ability of the stroma to not only contribute to, but potentially drive, the progression of cancerous cells into a highly aggressive and metastatic phenotype is a concept that has only recently begun to be appreciated. The stroma has been shown to undergo morphological alterations, recruit reactive fibroblasts, macrophages, and lymphocytes, increase secretion of growth factors, signaling molecules and proteases, induce new blood vessel formation, as well as, produce an altered extracellular matrix when associated with a transformed epithelium. Fibroblasts, in particular, have been shown to consistently undergo several changes in both morphology and expression profiles when present in the tumor microenvironment. One defining characteristic of these carcinoma-associated fibroblasts, or myofibroblasts, is the expression of fibroblast activation protein-alpha (FAP). FAP is a membrane-bound serine protease that has both dipeptidase, as well as, gelatinase and collagenase activity. FAP is not expressed in healthy adults, but has been shown to be selectively expressed on myofibroblasts in the stroma surrounding 90% of epithelial cancers examined, including 7/7 human prostate cancer specimens, with minimal to no expression in either cancerous epithelial or adjacent normal tissues. FAP has been implicated in tumor promotion through studies demonstrating increases in tumor incidence, growth, and microvessel density using in vivo models. In contrast, other studies have shown that expression of FAP decreased tumorigenicity in vivo suggesting that the physiologic response to FAP may be dependent upon the exact context of its expression.


Descriptors :   *FIBROBLASTS , *PROSTATE CANCER , DIAGNOSIS(MEDICINE) , PHYSIOLOGICAL EFFECTS , THERAPY , RESPONSE(BIOLOGY) , IN VIVO ANALYSIS , CELLS(BIOLOGY) , PROMOTION(ADVANCEMENT) , ADULTS , LYMPHOCYTES , MACROPHAGES , BLOOD VESSELS , SECRETION , PEPTIDE HYDROLASES , COLLAGENASE , METASTASIS , NEOPLASMS , EPITHELIUM , GROWTH(GENERAL)


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE