glioblastoma

Transforming growth factor beta 2 (TGF-β2) is a member of TGF-beta superfamily that shares a characteristic cysteine knot structure. Mice with TGF-β2 gene deletion show defects in development of cardiac, lung, craniofacial, limb, spinal column, eye, inner ear and urogenital systems. All TGF-β isoforms signal via the same heteromeric receptor complex, consisting of a ligand binding TGF-β receptor type II (TβR-II), and a TGF-β receptor type I (TβR-I). Signal transduction from the receptor to the nucleus is mediated via SMADs. TGF-β expression is found in cartilage, bone, teeth, muscle, heart, blood vessels, haematopoitic cells, lung, kidney, gut, liver, eye, ear, skin, and the nervous system.

Transforming growth factor beta-2 (TGF-β2) is a secreted protein which belongs to the TGF-beta family. It is known as a cytokine that performs many cellular functions and has a vital role during embryonic development. The precursor is cleaved into mature TGF-beta-2 and LAP, which remains non-covalently linked to mature TGF-beta-2 rendering it inactive. It is an extracellular glycosylated protein. It is known to suppress the effects of interleukin dependent T-cell tumors. Defects in TGFB2 may be a cause of non-syndromic aortic disease (NSAD).

TGF beta 2 Protein, Human, Recombinant (Avi), Biotinylated is expressed in HEK293 mammalian cells with N-Avi tag. The predicted molecular weight is 10-14 KDa and the accession number is P61812.

Cadherin-11 is a type II classical cadherin member of the cadherin superfamily of integral membrane proteins that mediate calcium-dependent cell-cell adhesion. Cadherins interact with themselves in a homophilic manner in connecting cells, and thus contribute to the sorting of heterogeneous cell types. Cadherin-11 contains five cadherin domains and is mainly expressed in the brain. Mature cadherin proteins consists of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small highly conserved C-terminal cytoplasmic domain. It is shown that Cadherin-11 is a viable molecular target for therapeutic intervention in Glioblastoma multiforme.

ADGRD1 (Adhesion G Protein-Coupled Receptor D1, also known as GPR133) is a Protein Coding gene. 4 alternatively spliced human isoforms have been reported. ADGRD1, an orphan member of the adhesion family of G-protein-coupled receptors, is a critical regulator of the response to hypoxia and tumor growth in Glioblastoma (GBM). ADGRD1 represents a novel molecular target in GBM and possibly other malignancies where hypoxia is fundamental to pathogenesis. Variations in the ADGRD1 locus are linked with differences in metabolism, human height, and heart frequency. ADGRD1 is a Gs protein-coupled receptor belonging to the class of adhesion GPCRs. The adhesion G-protein-coupled receptors (GPCRs), including GPR133, are membrane-bound proteins with long N termini containing multiple domains.

The interplay between glioma stem cells (GSCs) and the tumor microenvironment plays crucial roles in promoting malignant growth of glioblastoma (GBM), the most lethal brain tumor. WISP1 is preferentially expressed and secreted by GSCs. Silencing WISP1 markedly disrupts GSC maintenance, reduces tumor-supportive TAMs (M2), and potently inhibits GBM growth. WISP1 signals through Integrin α6β1-Akt to maintain GSCs by an autocrine mechanism and M2 TAMs through a paracrine manner.

Cadherin-11, also known as OSF-4, Osteoblast cadherin and CDH11, is a type II classical cadherin from the cadherin superfamily, integral membrane proteins that mediate calcium-dependent cell-cell adhesion. Cadherins interact with themselves in a homophilic manner in connecting cells, may thus contribute to the sorting of heterogeneous cell types. Cadherin-11 contains five cadherin domains and is mainly expressed in brain. Mature cadherin proteins consists of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. It is shown that cadherin-11 is a viable molecular target for therapeutic intervention in Glioblastoma multiforme.

EphB2, a receptor tyrosine kinase for ephrin ligands, is overexpressed in various cancers and plays an important role in tumor progression. EPHB2 promotes endothelial-mesenchymal transition (EMT) and elicits associated pathologic characteristics of glioblastoma multiforme (GBM) such as invasion and migration. EPHB2 is epigenetically overexpressed in hypoxia, a condition highly prevalent in malignancy. Furthermore, HIF-2α is required for EPHB2 stabilization by hypoxia.

Ephrin-A1 is a member of the A-type ephrin family of cell surface proteins that function as ligands for the A-type Eph receptor tyrosine kinase family. Ephrin-A1 can be induced by TNF and IL1B. Its expression levels can be down-regulated in primary glioma tissues compared to the normal tissues. The soluble monomeric form is expressed in the glioblastoma multiforme (GBM) and breast cancer cells. Soluble Ephrin-A1 is necessary for the transformation of HeLa and SK-BR3 cells and participates in the relocalization of EPHA2 away from sites of cell-cell contact during transformation. Ephrin-A1 plays an important role in angiogenesis and tumor neovascularization.

Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IkB alpha, NFKBIA, or IKBA), is a member of the NF-kappa-B inhibitor family that function to inhibit the NF-kB transcription factor. NFKBIA inhibits NF-kB by masking the nuclear localization signals (NLS) of NF-kB proteins and keeping them sequestered in an inactive state in the cytoplasm. Also, NFKBIA blocks the ability of NF-κB transcription factors to bind to DNA, which is required for NF-kB's proper functioning. Signal-induced degradation of I kappa B alpha exposes the nuclear localization signal of NF-kappa B, thus allowing it to translocate into the nucleus and activate transcription from responsive genes. An autoregulatory loop is established when NF-kappa B induces expression of the I kappa B alpha gene and newly synthesized I kappa B alpha accumulates in the nucleus where it negatively regulates NF-kappa B-dependent transcription. As part of this post-induction repression, the nuclear export signal on I kappa B alpha mediates the transport of NF-kappa B-I kappa B alpha complexes from the nucleus to the cytoplasm. Deletion of NFKBIA has an effect that is similar to the effect of EGFR amplification in the pathogenesis of glioblastoma and is associated with comparatively short survival. Polymorphisms in NFKBIA may be important in pre-disposition to and outcome after treatment, of multiple myeloma (MM). The NFKBIA gene product, IkappaBalpha, binds to NF-kappaB preventing its activation and is important in mediating resistance to apoptosis in B-cell lymphoproliferative diseases.

Human Brain-Specific Angiogenesis Inhibitor 3 (BAI3) is a 177 kDa seven-span transmembrane (TM) protein, which is thought to be a member of the secretin receptor family. It is synthesized by neurons of the CNS and likely is a negative regulator of angiogenesis. BAI3 is 1498 amino acids in size. It contains three distinct regions: an N-terminal extracellular domain (ECD) (aa25-883), a 7-TM segment, and a C-terminal cytoplasmic region. The ECD contains four antiangiogenic TSP type 1 repeat (aa296-508), and one GSP domain (aa 816-867) that is likely used to cleave the ECD from the membrane-bound receptor. There is one altermate splice form that shows a deletion of aa 643-665. Over aa 25-880, human BAI3 shares 98% aa identity with mouse BAI3. BAI3 has been reported primarily in the brain, but is also localized to lung, testis, and pancreas. It might be involved in angiogenesis inhibition and suppression of glioblastoma.

Deleted in malignant brain tumors 1 protein, also known as glycoprotein 34, surfactant pulmonary-associated D-binding protein, DMBT1 and GP34, is a secreted protein which belongs to theDMBT1 family. DMBT1 contains 2CUB domains, 14SRCR domains and 1ZP domain. It is highly expressed in alveolar and macrophage tissues. In some macrophages, expression is detected on the membrane, and in other macrophages, it is strongly expressed in the phagosome/phagolysosome compartments. Defects in DMBT1 are involved in the development of glioma (GLM). Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas , and ependymomas. DMBT1 may be considered as a candidate tumor suppressor for brain, lung, esophageal, gastric, and colorectal cancers. It may play roles in mucosal defense system, cellular immune defense and epithelial differentiation. DMBT1 may play a role as an opsonin receptor for SFTPD and SPAR in macrophage tissues throughout the body, including epithelial cells lining the gastrointestinal tract. It may be an important factor in fate decision and differentiation of transit-amplifying ductular (oval) cells within the hepatic lineage. DMBT1 may function as a binding protein in saliva for the regulation of taste sensation. It binds to HIV-1 envelope protein and has been shown to both inhibit and facilitate viral transmission.