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Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

SEMA3F, isolated from a 3p21.3 deletion, has antitumor activity in transfected cells, and protein expression correlates with tumor stage and histology. In primary tumors, SEMA3F and VEGF surface staining is inversely correlated. Coupled with SEMA3F at the leading edge of motile cells, we previously suggested that both proteins competitively regulate cell motility and adhesion. We have investigated this using the breast cancer cell line, MCF7. SEMA3F inhibited cell attachment and spreading as evidenced by loss of lamellipodia extensions, membrane ruffling, and cell-cell contacts, with cells eventually rounding-up and detaching. In contrast, VEGF had opposite effects. Although SEMA3F binds NRP2 with 10-fold greater affinity than NRP1, the effects in MCF7 were mediated by NRP1. This was determined by receptor expression and blocking of anti-NRP1 antibodies. Similar effects, but through NRP2, were observed in the C100 breast cancer cell line. Although we were unable to demonstrate changes in total GTP-bound Rac1 or RhoA, we did observe changes in the localization of Rac1-GFP using time lapse microscopy. Following SEMA3F, Rac1 moved to the base of lamellipodia and - with their collapse - to the membrane. These results support the concept that SEMA3F and VEGF have antagonistic actions affecting motility in primary tumor cell.
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PMID:Semaphorin SEMA3F and VEGF have opposing effects on cell attachment and spreading. 1265 73

Neuropilins (NRP) are receptors for the class 3 semaphorin (SEMA3) family of axon guidance molecules and the vascular endothelial growth factor (VEGF) family of angiogenesis factors. Although the seminal studies on SEMA3s and NRPs first showed them to be mediators of axon guidance, it has become very apparent that these proteins play an important role in vascular and tumor biology as well. Neuronal guidance and angiogenesis are regulated similarly at the molecular level. For example, SEMA3s not only repel neurons and collapse axon growth cones, but have similar effects on endothelial cells and tumor cells. Preclinical studies indicate that SEMA3F is a potent inhibitor of tumor angiogenesis and metastasis. In addition, neutralizing antibodies to NRP1 enhance the effects of anti-VEGF antibodies in suppressing tumor growth in xenograft models. This article reviews NRP and SEMA3 structural interactions and their role in developmental angiogenesis, tumor angiogenesis and metastasis based on cell culture, zebrafish and murine studies.
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PMID:Targeting endothelial and tumor cells with semaphorins. 1776 98

Class three semaphorins (SEMAs) were originally shown to be mediators of axon guidance that repelled axons and collapsed growth cones, but it is now evident that SEMA3F, for example, has similar effects on tumor cells and endothelial cells (EC). In both human U87MG glioma cells and human umbilical vein EC, SEMA3F induced rapid cytoskeletal collapse, suppressed cell contractility, decreased phosphorylation of cofilin, and inhibited cell migration in culture. Analysis of the signaling pathways showed that SEMA3F formed a complex with NRP2 (neuropilin-2) and plexin A1. These interactions eventually led to inactivation of the small GTPase, RhoA, which is necessary for stress fiber formation and cytoskeleton integrity. A novel upstream RhoA mediator was shown to be ABL2, also known as ARG, a membrane-anchored nonreceptor tyrosine kinase. Within minutes after the addition of SEMA3F, ABL2 directly bound plexin A1 but not to a plexin A1 mutant lacking the cytoplasmic domain. In addition, ABL2 phosphorylated and thereby activated p190RhoGAP, which inactivated RhoA (GTP to GDP), resulting in cytoskeleton collapse and inhibition of cell migration. On the other hand, cells overexpressing an ABL2 inactive kinase mutant or treated with ABL2 small interfering RNA did not inactivate RhoA. Cells treated with p190RhoGAP small interfering RNA also did not inactivate RhoA. Together, these results suggested that ABL2/ARG is a novel mediator of SEMA3F-induced RhoA inactivation and collapsing activity.
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PMID:ABL2/ARG tyrosine kinase mediates SEMA3F-induced RhoA inactivation and cytoskeleton collapse in human glioma cells. 1866 May 2

Class 3 semaphorins (SEMA3) are mediators of neuronal guidance first shown to repel axons and collapse axonal growth cones by depolymerization of cytoskeletal F-actin. Subsequently, it was found that SEMA3 could also mediate angiogenesis. SEMA3F binds to its receptor, neuropilin 2 (NRP2), a transmembrane protein expressed on neurons, EC (EC), and tumor cells. In vitro, SEMA3F collapses the F-actin cytoskeleton, repels EC, and inhibits EC and tumor cell adhesion and migration in a manner similar to what occurs with axons. In a mouse tumor model, SEMA3F is a potent inhibitor of tumor angiogenesis, tumor progression, and metastasis. SEMA3F is encoded in a region of chromosome 3p21.3 that is commonly deleted in small cell lung cancers, suggesting that SEMA3F is a tumor suppressor. SEMA3F may have therapeutic potential. Therefore, this chapter is focused primarily on the detailed methods to purify SEMA3F and to assay its biologic activity, including cytoskeleton collapse and repulsion.
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PMID:Semaphorin-induced cytoskeletal collapse and repulsion of endothelial cells. 1877 22

Class 3 semaphorins (SEMA3) were first identified as glycoproteins that negatively mediate neuronal guidance by binding to neuropilin and repelling neurons away from the source of SEMA3. However, studies have shown that SEMA3s are also secreted by other cell types, including tumor cells, where they play an inhibitory role in tumor growth and angiogenesis (specifically SEMA3B and SEMA3F). SEMA3s primarily inhibit the cell motility and migration of tumor and endothelial cells by inducing collapse of the actin cytoskeleton via neuropilins and plexins. Besides binding to SEMA3s, neuropilin also binds the protumorigenic and proangiogenic ligand vascular endothelial growth factor (VEGF). Although some studies attribute the antitumorigenic and antiangiogenic properties of SEMA3s to competition between SEMA3s and VEGF for binding to neuropilin receptors, several others have shown that SEMA3s display growth-inhibitory activity independent of competition with VEGF. A better understanding of these molecular interactions and the role and signaling of SEMA3s in tumor biology will help determine whether SEMA3s represent potential therapeutic agents. Herein, we briefly review (a) the role of SEMA3s in mediating tumor growth, (b) the SEMA3 receptors neuropilins and plexins, and (c) the potential competition between SEMA3s and VEGF family members for neuropilin binding.
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PMID:Role of class 3 semaphorins and their receptors in tumor growth and angiogenesis. 1988 79

Class 3 semaphorins were discovered as a family of axon guidance molecules, but are now known to be involved in diverse biologic processes. In this study, we investigated the anti-angiogenic potential of SEMA3E and SEMA3F (SEMA3E&F) in infantile hemangioma (IH). IH is a common vascular tumor that involves both vasculogenesis and angiogenesis. Our lab has identified and isolated hemangioma stem cells (HemSC), glucose transporter 1 positive (GLUT1(+)) endothelial cells (designated as GLUT1(sel) cells) based on anti-GLUT1 magnetic beads selection and GLUT1-negative endothelial cells (named HemEC). We have shown that these types of cells play important roles in hemangiogenesis. We report here that SEMA3E inhibited HemEC migration and proliferation while SEMA3F was able to suppress the migration and proliferation in all three types of cells. Confocal microscopy showed that stress fibers in HemEC were reduced by SEMA3E&F and that stress fibers in HemSC were decreased by SEMA3F, which led to cytoskeletal collapse and loss of cell motility in both cell types. Additionally, SEMA3E&F were able to inhibit vascular endothelial growth factor (VEGF)-induced sprouts in all three types of cells. Further, SEMA3E&F reduced the level of p-VEGFR2 and its downstream p-ERK in HemEC. These results demonstrate that SEMA3E&F inhibit IH cell proliferation and suppress the angiogenic activities of migration and sprout formation. SEMA3E&F may have therapeutic potential to treat or prevent growth of highly proliferative IH.
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PMID:Infantile hemangioma-derived stem cells and endothelial cells are inhibited by class 3 semaphorins. 2608 95