Disease relevance of BCAN

• Novel tumor-specific isoforms of BEHAB/brevican identified in human malignant gliomas [1].
• B/b(Deltag) lacks most of the carbohydrates typically present on BEHAB/brevican and is the major up-regulated isoform of this protein in high-grade gliomas but is absent in a specific subset of low-grade, indolent oligodendrogliomas [1].
• Brevican, an important extracellular proteoglycan that is upregulated in glioblastomas, can be degraded by certain proteases [2].
• The up-regulation of BEHAB/brevican in response to CNS injury suggests a role for this extracellular matrix molecule in reactive gliosis [3].
• BEHAB/brevican expression is also upregulated during periods of increased glial cell motility in development and following brain injury [4].

High impact information on BCAN

• Thus far these proteoglycans include versican, neurocan, and brevican [5].
• BEHAB/brevican: a brain-specific lectican implicated in gliomas and glial cell motility [6].
• Here we describe for the first time the expression of BEHAB/brevican in human brain and characterize two novel glioma-specific isoforms, B/b(sia) and B/b(Deltag), which are generated by differential glycosylation and are absent from normal adult brain and other neuropathologies [1].
• A role for this protein in glioma cell invasion was tested by transfecting a noninvasive cell line with the BEHAB/brevican gene [7].
• Similar aggregates (potentially containing new members of the link protein family), in which other chondroitin sulfate proteoglycans (i.e. versican, brevican, and neurocan) substitute for aggrecan, may contribute to the structural integrity of many other tissues including skin and brain [8].

Chemical compound and disease context of BCAN

• One ECM molecule that shows dramatic upregulation in gliomas is BEHAB (brain enriched hyaluronan binding)/brevican, a brain-specific chondroitin sulfate proteoglycan [4].

Biological context of BCAN

• Human BRAL1 and BCAN genes that belong to the link-module superfamily are tandemly arranged on chromosome 1q21-23 [9].
• Interestingly, the polypeptide deduced from the open reading frame of the 3.3-kb transcript is truncated just carboxyl-terminal of the central domain of brevican and instead contains a putative glypiation signal [10].
• Fourth, we confirm and extend previous studies from our laboratory, here demonstrating the upregulation of BEHAB/brevican mRNA in human glioma quantitatively [11].
• First, BEHAB/brevican maps to human chromosome 1q31 [11].
• No cDNAs encoding a GPI-anchored bcan variant could be isolated from that cDNA library [12].

Anatomical context of BCAN

• Brevican is a member of the lectican family of chondroitin sulfate proteoglycans that is predominantly expressed in the central nervous system [13].
• Northern blot analysis reveals that a single 3.3-kilobase brevican transcript is present predominantly in the brain, and that it is expressed in primary cerebellar astrocytes but not in neurons [14].
• In marked contrast, the highly invasive CNS-1 glioma cell line expresses and cleaves BEHAB/brevican protein when grown as an intracranial graft [15].
• The aggregating proteoglycans (aggrecan, versican, neurocan, and brevican) are important components of many extracellular matrices [16].
• In contrast to the competition described above, TN-R cooperates with brevican and neurocan to induce attachment of tectal cells and neurite outgrowth, probably by forming a bridge between the lectican substrate and contactin 1 as the neuronal receptor [17].

Associations of BCAN with chemical compounds

• Brevican, a chondroitin sulfate proteoglycan of rat brain, occurs as secreted and cell surface glycosylphosphatidylinositol-anchored isoforms [10].
• Antibodies raised against a bacterially expressed glutathione S-transferase-brevican fusion protein have been used to show that both soluble and membrane-bound brevican isoforms exist [10].
• This proteoglycan, named brevican, carries chondroitin sulfate chains, and, like other members of the family, contains a hyaluronic acid-binding domain in its N-terminal region, an epidermal growth factor-like repeat, a lectin-like and a complement regulatory protein-like domains in its C-terminal region [14].
• The highest decomposition rate is shown by DCAN, followed by BCAN and DBAN, while at the presence of sodium thiosulfate the decomposition of DBAN is the fastest [18].
• The concentrations of dichloroacetonitrile (CHCl2CN, DCAN), bromochloroacetonitrile (CHBrClCN, BCAN) and dibromoacetonitrile (CHBr2CN, DBAN) were determined by a gas chromatography mass spectrometry (GC-MS) method at regular time intervals and different temperatures [18].

Other interactions of BCAN

• Brevican is degraded by matrix metalloproteinases and aggrecanase-1 (ADAMTS4) at different sites [13].
• Molecular cloning of brevican, a novel brain proteoglycan of the aggrecan/versican family [14].
• These observations suggest that brevican may play a role in maintaining the extracellular environment of mature brain as a major constituent of the adult brain extracellular matrix [19].
• Aggrecan, versican, neurocan, and brevican are important components of the extracellular matrix in various tissues [20].
• Aggrecan, brevican and neurocan inhibit the effects of TN-R on microprocess formation and growth cone size [17].

Analytical, diagnostic and therapeutic context of BCAN

• We herein determined by fluorescence in situ hybridization the chromosomal localization of 2 human genes, BRAL1 and BCAN, both of which belong to the link-module superfamily, i.e. to the same band of chromosome 1q21-23 [9].
• NH(2)-terminal sequence analyses of the digestion fragments revealed that cleavages of the brevican core protein by these metalloproteinases occurred commonly within the central non-homologous domain [13].
• In this study, we found that secreted brevican transcript was detectable in the pituitary of both male and female adult rats by reverse transcriptase-polymerase chain reaction (RT-PCR) amplification [21].
• Surface plasmon resonance analysis revealed that brevican lectin has at least a 10-fold higher affinity than the other lectican lectins [22].
• Glioma cell lines maintained under standard cell culture conditions or grown as s.c. tumors do not express BEHAB [23].

References