Disease relevance of NOV

• As nov expression has been shown to be altered in both avian and human nephroblastomas and to be a target of WT1 regulation, NOV may play important roles in normal nephrogenesis and the development of Wilms' tumors [1].
• Altered expression of CCN3 has been observed in a variety of tumors, including hepatocellular carcinomas, Wilm's tumors, Ewing's sarcomas, gliomas, rhabdomyosarcomas, and adrenocortical carcinomas [2].
• CCN3 expression was found in 15 of 45 Ewing's sarcoma tissue samples [3].
• In particular, we did not observe any expression of CCN3 in the 15 primary tumors that did not develop metastases [3].
• The concentration of NOVH was significantly decreased in patients suffering from astrocytomas or multiple sclerosis, two diseases of the nervous system [4].

High impact information on NOV

• The connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed (CCN) family [5].
• The C-terminal domain of the regulatory protein NOVH is sufficient to promote interaction with fibulin 1C: a clue for a role of NOVH in cell-adhesion signaling [6].
• Two members of the family (CYR61 and CTGF) are positive regulators of cell proliferation, whereas NOVH and two other members (ELM1 and RCOP-1) exhibit features of negative regulators of growth [6].
• Although not mitogenic on its own, CCN3 also enhances basic fibroblast growth factor-induced DNA synthesis [7].
• Integrin-dependent functions of the angiogenic inducer NOV (CCN3): implication in wound healing [7].

Chemical compound and disease context of NOV

• Twenty-two patients affected by relapsed or refractory non-Hodgkin's lymphoma (NHL) were treated with a combination of ifosfamide (IFO) at the dose of 1.2 g/m2 intravenous (i.v.) (1 h infusion) for 5 consecutive days with mesna as uroprotector plus mitoxantrone (NOV) at the dose of 12 mg/m2 i.v. on day 1; both drugs were recycled every 3-4 weeks [8].

Biological context of NOV

• These data suggest that NOV can act as a growth factor for some cells and binds to a specific receptor that leads to the phosphorylation of a 221 kDa protein [9].
• We have isolated the rat NOV gene, and the DNA sequence shares 90% identity with the mouse and 80% identity with the human sequences [9].
• These results set the stage for a study of NOVH-fibulin 1C interactions and their potential significance in cell-adhesion signaling in normal and pathological conditions [6].
• In contrast, CCN3-induced cell migration is dependent on integrins alphavbeta3 and alpha5beta1, whereas alpha6beta1 does not play a role in this process [2].
• Purified CCN3 supports primary skin fibroblast adhesion through integrins alpha(5)beta(1) and alpha(6)beta(1) and induces fibroblast chemotaxis through integrin alpha(v)beta(5) [7].

Anatomical context of NOV

• Examination of NOV expression in various human cell lines revealed that NOV was expressed in U87, 293, T98G, SK-N-MC and Hs683 but not in HepG2, HL60, THP1 and Jurkat [9].
• When 3T3 fibroblasts were treated with this recombinant NOV protein, a dose-dependent increase in proliferation was observed [9].
• Higher levels of rat NOV mRNA were seen in the brain, lung and skeletal muscle compared to the other tissues [9].
• Analysis of tyrosine-phosphorylated proteins revealed that when 3T3 cells were treated with NOV, a 221 kDa protein was phosphorylated [9].
• The rat NOV gene was expressed in all rat tissues examined, including brain, lung, heart, kidney, liver, spleen, thymus and skeletal muscle [9].

Associations of NOV with chemical compounds

• Nephroblastoma overexpressed gene (NOV) codes for a growth factor that induces protein tyrosine phosphorylation [9].
• Mechanistically, CCN3 supports human umbilical vein endothelial cell adhesion through multiple cell surface receptors, including integrins alphavbeta3, alpha5beta1, alpha6beta1, and heparan sulfate proteoglycans [2].
• In C2/4 myogenic cells, elevated expression of NOV led to down-regulation of MyoD and myogenin, resulting in inhibition of myotube formation [10].
• However, 7 days after injury, NOV expression is down-regulated, except near the luminal surface of the developing intima, where it is strongly expressed [11].
• HUVEC adhesion to NOV caused intracellular signalling, as evidenced by increased phosphotyrosine content of focal adhesion kinase [11].

Regulatory relationships of NOV

• There is a possibility that the regulation of NOV expression is different from the pathway regulated by WT1 [12].
• We also show that the induction of MMP3 in cells expressing NOVH is potentiated by either cell density, serum, or PDGF-BB [13].

Other interactions of NOV

• Decreased expression of the angiogenic regulators CYR61 (CCN1) and NOV (CCN3) in human placenta is associated with pre-eclampsia [14].
• HES1, a target of Notch, previously proposed to mediate NOV action, was not implicated in the inhibition of differentiation [15].
• Expressions of cysteine-rich61, connective tissue growth factor and Nov genes in hepatocellular carcinoma and their clinical significance [16].
• The human NOV secreted glycoprotein (NOVH) is abundant in the fetal and adult adrenal cortex [17].
• Binding properties and distribution of insulin-like growth factor binding protein-related protein 3 (IGFBP-rP3/NovH), an additional member of the IGFBP Superfamily [18].

Analytical, diagnostic and therapeutic context of NOV

• Characterization of human NOV in biological fluids: an enzyme immunoassay for the quantification of human NOV in sera from patients with diseases of the adrenal gland and of the nervous system [4].
• PTHrP treatment (which inhibits terminal differentiation) decreased NOV expression in murine femurs maintained in organ culture, and decreased the activity of a NOV reporter construct in vitro [19].
• Reverse transcription polymerse chain reaction (RT-PCR) was used to detect the mRNA expression levels of Cyr61, CTGF and Nov genes in 31 resected specimens of hepatocellular carcinoma and para-cancerous normal liver tissues semi-quantitatively and the relation between their expression levels and clinical pathological parameters were compared [16].
• Confocal microscopy was used to visualise the nuclear NOV protein in HeLa and 143 cells [20].
• Western blotting analysis of NOV proteins in both types of fractions was performed using two NOV specific antibodies [20].

References