Rabbit anti-Human ITGA10 polyclonal antibody

Central nervous system (CNS) relapse is a devastating complication that occurs in about 5% of diffuse large B-cell lymphoma (DLBCL) patients. Currently, there are no predictive biological markers. We wanted to study potential biomarkers of CNS tropism that play a role in adhesion, migration and/or in the regulation of inflammatory responses. The expression levels of ITGA10, CD44, PTEN, cadherin-11, CDH12, N-cadherin, P-cadherin, lactoferrin and E-cadherin were studied with IHC and IEM. GEP was performed to see whether found expressional changes are regulated at DNA/RNA level. IHC included 96 samples of primary CNS lymphoma (PCNSL), secondary CNS lymphoma (sCNSL) and systemic DLBCL (sDLBCL). IEM included two PCNSL, one sCNSL, one sDLBCL and one reactive lymph node samples. GEP was performed on two DLBCL samples, one with and one without CNS relapse. CNS disease was associated with enhanced expression of cytoplasmic and membranous ITGA10 and nuclear PTEN (P < 0.0005, P = 0.002, P = 0.024, respectively). sCNSL presented decreased membranous CD44 and nuclear and cytoplasmic cadherin-11 expressions (P = 0.001, P = 0.006, P = 0.048, respectively). In PCNSL lactoferrin expression was upregulated (P < 0.0005). IEM results were mainly supportive of the IHC results. In GEP CD44, cadherin-11, lactoferrin and E-cadherin were under-expressed in CNS disease. Our results are in line with previous studies, where gene expressions in extracellular matrix and adhesion-related pathways are altered in CNS lymphoma. This study gives new information on the DLBCL CNS tropism. If further verified, these markers might become useful in predicting CNS relapses.

Orbital venous malformation results from the aberrant angiogenesis in the orbit; however, the detailed molecular mechanism is still not clear. In this study, tissue samples from 27 patients with orbital venous malformation were collected and subjected to whole exome sequencing. Melanocortin 4 receptor was the gene with highest incidence (7/27) of mutation identified in this series. A total of four types of mutations were found in the coding region and the 5MODIFIER LETTER PRIME-untranslated region of melanocortin 4 receptor. All these mutations resulted in the upregulation of melanocortin 4 receptor expression. In vitro assays using human umbilical vein endothelial cells demonstrated that the endothelial properties including cell proliferation, cell cycle, cell migration, and tube formation are positively correlated with the expression level of melanocortin 4 receptor. Melanocortin 4 receptor mutations resulted in increased cAMP production in a cell-based assay. By RNA sequencing technique, melanocortin 4 receptor was found to modulate the downstream genes of PI3K/AKT/mTOR pathway, including p21, cyclin B1, ITGA10, and ITGA11, which are known to regulate the endothelial properties. These data demonstrated that mutations in melanocortin 4 receptor modulate the downstream signaling pathway, facilitate the angiogenic activity of endothelial cells, and therefore is one potential mechanism of orbital venous malformation pathogenesis. Impact statement The detailed molecular mechanism of orbital venous malformation (OVM) is still not clear. Using whole exome sequencing, 4 types of melanocortin 4 receptor (MC4R) mutation were detected in 7 of 27 patients with OVM, and all types of MC4R mutations resulted in the upregulation of MC4R expression. In vitro study indicated that MC4R has impacts on the proliferation, cell cycle, migration, and tube formation of the endothelial cells. Moreover, MC4R mutations altered the downstream signaling, including cAMP concentration and the expression levels of several PI3K/AKT/mTOR downstream genes, including p21, cyclin B1, ITGA10, and ITGA11. MC4R mutations may lead to the pathogenesis of OVM through modulating the downstream signaling to alter the angiogenic activity of endothelial cells.