Soft tissue sarcomas (STSs) are a heterogeneous group of mesenchymal tumors of >50 subtypes. However, STSs represent <1% of types of cancer. Despite this low frequency, the disease is aggressive and treatment, when possible, is based on traditional chemotherapies. A number of cases of resistance to adjuvant therapies have been reported. Metastases are commonly identified in STS patients during ...

CD100 represents the first semaphorin described in the immune system. It is expressed as a 300-kDa homodimer at the surface of most hematopoietic cells, but is also found in a soluble form following a proteolytic cleavage upon cell activation. We herein established that soluble CD100 (sCD100) impaired the migration of human monocytes and immature dendritic cells (DCs), but not of mature DCs. Pe...

Proper circuit function in the mammalian nervous system depends on the precise assembly and development of excitatory and inhibitory synaptic connections between neurons. Through a loss-of-function genetic screen in cultured hippocampal neurons, we previously identified the class 4 Semaphorin Sema4D as being required for proper GABAergic synapse development. Here we demonstrate that Sema4D is s...

CONTEXT AND OBJECTIVE The etiology of miscarriage is often multifactorial. One major cause, immunological rejection of the fetus, has not been clearly elucidated. Our aim was to establish whether the semaphorin CD100, its natural receptor CD72, and the glycoprotein CD45, implicated in immune mechanisms, are involved in pregnancy loss by examining their placental expression with real-time PCR, i...

Hemostatic thrombi develop a characteristic architecture in which a core of highly activated platelets is covered by a shell of less-activated platelets. Here we have used a systems biology approach to examine the interrelationship of this architecture with transport rates and agonist distribution in the gaps between platelets. Studies were performed in mice using probes for platelet accumulati...

Semaphorins were identified originally as guidance cues for developing neuronal axons. However, it is becoming clear that several semaphorins play important roles in the immune system. For instance, Sema4D (CD100) enhances activation of B cells and dendritic cells through its receptor, CD72. Sema4A is crucially involved not only in T cell priming but also in Th1/Th2 regulation. Additional semap...

Semaphorin 4D is highly expressed at the invasive tumor margin and acts as a guidance molecule, restricting movement of tumoricidal immune cells into the tumor microenvironment. We recently showed that antibody neutralization of SEMA4D augmented activated monocyte and anticancer T-cell tumor penetration and that anti-SEMA4D antibody potentiated other immunomodulatory therapies in murine tumor m...

The semaphorin family comprises soluble and membrane-bound proteins originally identified as axonal guidance cues that function during neuronal development. Emerging evidence suggests that a subset of semaphorins, called 'immune semaphorins', function in the immune system. The class IV semaphorins Sema4D/CD100 and Sema4A use CD72 and Tim-2, respectively, as receptors during immune responses; th...