TY - JOUR
T1 - Role of class 3 semaphorins and their receptors in tumor growth and angiogenesis
AU - Gaur, Puja
AU - Bielenberg, Diane R.
AU - Samuel, Shaija
AU - Bose, Debashish
AU - Zhou, Yunfei
AU - Gray, Michael J.
AU - Dallas, Nikolaos A.
AU - Fan, Fan
AU - Xia, Ling
AU - Lu, Jia
AU - Ellis, Lee M.
PY - 2009/11/15
Y1 - 2009/11/15
N2 - Class 3 semaphorins (SEMA3) were first identified as glycoproteins that negatively mediate neuronal guidance bybinding to neuropilin and repelling neurons awayfrom the source of SEMA3. However, studies have shown that SEMA3s are also secreted by other cell types, including tumor cells, where theypl ayan inhibitoryrole in tumor growth and angiogenesis (specificallySEMA3B and SEMA3F). SEMA3s primarilyinhibit the cell motilityand migration of tumor and endothelial cells byinducing 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 displaygrowthinhibitoryactivity independent of competition with VEGF. A better understanding of these molecular interactions and the role and signaling of SEMA3s in tumor biologywill help determine whether SEMA3s represent potential therapeutic agents. Herein, we brieflyreview (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.
AB - Class 3 semaphorins (SEMA3) were first identified as glycoproteins that negatively mediate neuronal guidance bybinding to neuropilin and repelling neurons awayfrom the source of SEMA3. However, studies have shown that SEMA3s are also secreted by other cell types, including tumor cells, where theypl ayan inhibitoryrole in tumor growth and angiogenesis (specificallySEMA3B and SEMA3F). SEMA3s primarilyinhibit the cell motilityand migration of tumor and endothelial cells byinducing 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 displaygrowthinhibitoryactivity independent of competition with VEGF. A better understanding of these molecular interactions and the role and signaling of SEMA3s in tumor biologywill help determine whether SEMA3s represent potential therapeutic agents. Herein, we brieflyreview (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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U2 - 10.1158/1078-0432.CCR-09-1810
DO - 10.1158/1078-0432.CCR-09-1810
M3 - Review article
C2 - 19887479
AN - SCOPUS:72549108629
SN - 1078-0432
VL - 15
SP - 6763
EP - 6770
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 22
ER -