Disease relevance of Glmn

• Human FAP is selectively expressed by tumor stromal fibroblasts in epithelial carcinomas, but not by epithelial carcinoma cells, normal fibroblasts, or other normal tissues [1].
• Both s.c. implanted tumors and lung metastases were susceptible to anti-FAP immunotherapy [2].
• Using melanoma, carcinoma, and lymphoma models, we show that tumor growth was inhibited in tumor-bearing mice vaccinated against FAP and that the magnitude of the antitumor response was comparable to that of vaccination against tumor cell-expressed antigens [2].
• In accordance with a strict target-selective activity of sc40-FasL, the intravenous application of this reagent in mice revealed no signs of systemic toxicity and prevented growth of xenotransplanted FAP-positive (but not FAP-negative) tumor cells [3].
• The primary objective of this study was to evaluate the clinical significance of stromal FAP in human colon cancers by immunohistochemisty [4].

High impact information on Glmn

• To specifically kill tumor-associated fibroblasts, we constructed an oral DNA vaccine targeting fibroblast activation protein (FAP), which is specifically overexpressed by fibroblasts in the tumor stroma [5].
• No morbidity or mortality was associated with anti-FAP vaccination except for a small delay in wound healing [2].
• Mice were immunized against fibroblast activation protein (FAP), a product up-regulated in tumor-associated fibroblasts, using dendritic cells transfected with FAP mRNA [2].
• Fibroblast activation protein (FAP) is a type II integral membrane glycoprotein belonging to the serine protease family [1].
• Thus, sc40-FasL efficiently induced apoptosis only in FAP-expressing cells [3].

Biological context of Glmn

• The high expression of glomulin in murine vasculature suggests an important role for glomulin in blood vessel development and/or maintenance, which is supported by the vascular phenotype seen in GVM patients with mutations in this gene [6].
• The predicted amino acid sequence for FAP-B shows 61% and 71% homology, respectively, with Mycobacterium avium FAP (FAP-A) and Mycobacterium leprae FAP (FAP-L) [7].
• Truncating mutations in the tumour suppressor gene adenomatous polyposis coli (APC) are early and important events, both in inheritable (familial adenomatous polyposis, FAP) and spontaneous forms of intestinal cancer [8].
• In order to delineate the promoter elements mediating the transcriptional activation, constructs which lack the FAP and the CRE sites but contain an intact SRE were co-transfected with the ras construct [9].
• Fibroblast activation protein (FAP) is upregulated in myelomatous bone and supports myeloma cell survival [10].

Anatomical context of Glmn

• Glomulin is predominantly expressed in vascular smooth muscle cells in the embryonic and adult mouse [6].
• Fibroblast activation protein (FAP) is a cell surface antigen of reactive tumor stromal fibroblasts found in epithelial cancers and in granulation tissue during wound healing [11].
• Immunohistochemical analysis of myelomatous bone sections revealed FAP expression by osteoclasts, osteogenic cells, fibrotic stroma and certain adipocytes and vascular endothelial cells [10].
• Antigens and receptors that are highly expressed on tumor stromal cells, such as fibroblast activation protein (FAP), are attractive targets for antibody-based therapies because the supporting stroma and vessel network is essential for a solid neoplasm to grow beyond a size of 1-2 mm [12].

Associations of Glmn with chemical compounds

• Mutation of the putative catalytic serine residue of FAP to alanine abolishes both enzymatic activities [11].
• We examined the age-dependent susceptibility to azoxymethane (AOM)-induced and spontaneous tumorigenesis in the Min/+ mouse, a murine FAP model [13].
• One of the fractions, FAP (fraction from apple polyphenol) 1, which contains non-catechin polyphenols, did not significantly inhibit the CT-catalyzed ADP-ribosylation of agmatine [14].
• The model was subsequently used to evaluate the biodistribution properties of an iodine-131-labeled humanized anti-FAP monoclonal antibody (BIBH-7) [12].
• Doxycycline disrupts transthyretin amyloid: evidence from studies in a FAP transgenic mice model [15].

Analytical, diagnostic and therapeutic context of Glmn

• We studied glomulin expression during murine development (E9.5 days post-coitum until adulthood) by non-radioactive in situ hybridization [6].
• HT-29 xenografts treated with these inhibitory anti-FAP antisera exhibited attenuated growth compared with tumors treated with preimmunization rabbit antisera [1].
• These data demonstrate the ability of FAP to potentiate tumor growth in an animal model [1].
• These data warrant transfer of the anti-FAP-TNF immunocytokine into clinical trials for the treatment of FAP-positive tumors [16].
• Consistent with its in vivo expression pattern determined by immunohistochemistry, FAP enzyme activity was detected by an immunocapture assay in human cancerous tissues but not in matched normal tissues [11].

References