Semaphorin 7A Promotes Angiogenesis in an Experimental Corneal Neovascularization Model

Ghanem, Ramon Coral; Han, Kunsoo; Rojas, Juan J.; Ozturk, Okan; Kim, David J.; Jain, Sandeep; Chang, Jin Hong; Azar, Dimitri T.

doi:10.3109/02713683.2011.593730

Cited by 33 publications

(24 citation statements)

References 30 publications

(27 reference statements)

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“…This logic led to the identification of several class-3 semaphorins such as sema3F as inhibitors of tumor angiogenesis and tumor progression and to their consideration as potential therapeutics for the treatment of cancer. 92,102,103 In contrast with the class-3 semaphorins, of which most have been characterized as anti-angiogenic and antitumorigenic factors, semaphorins such as sema4D, 104,105 sema5A, 106,107 sema6A, 108 sema4A 109 and sema7A 110 have been described as promoters of angiogenesis and as promoters of tumor progression. Such semaphorins are therefore considered as targets for the development of novel cancer therapeutics.…”

Section: Semaphorins As Regulators Of Tumor Progressionmentioning

confidence: 99%

The role of the semaphorins in cancer

Neufeld

Mumblat

Smolkin

et al. 2016

Cell Adhesion & Migration

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The semaphorins were initially characterized as axon guidance factors, but have subsequently been implicated also in the regulation of immune responses, angiogenesis, organ formation, and a variety of additional physiological and developmental functions. The semaphorin family contains more then 20 genes divided into 7 subfamilies, all of which contain the signature sema domain. The semaphorins transduce signals by binding to receptors belonging to the neuropilin or plexin families. Additional receptors which form complexes with these primary semaphorin receptors are also frequently involved in semaphorin signaling. Recent evidence suggests that semaphorins also fulfill important roles in the etiology of multiple forms of cancer. Some semaphorins have been found to function as bona-fide tumor suppressors and to inhibit tumor progression by various mechanisms while other semaphorins function as inducers and promoters of tumor progression. The semaphorin familyThe semaphorin family members are divided into 8 subclasses of which subclasses 1 and 2 contain invertebrate semaphorins while subclasses 3-7 contain the 22 vertebrate semaphorins. The 8th subclass contains viral semaphorins. In early publications, semaphorins were assigned confusing names. This situation was rectified by the adoption of a unified nomenclature in which sema is followed by the subclass number and by alphabetic designation within the subclass.1 Semaphorins are characterized by the presence of a »500 amino-acids long sema domain located close to their N-termini which is also present in semaphorin receptors of the plexin family, and by a plexin-semaphorin-integrin (PSI) domain located downstream to the sema domain. The sema domain is essential for semaphorin activity and plays a role in the determination of the receptor binding specificity.2 The sema domains of several different semaphorins were characterized by X-ray crystallography revealing a b propeller topology.3-5 Different semaphorin subclasses are characterized by class specific structural motifs. Thus, the vertebrate semaphorins belonging to classes 3, 4 and 7 contain immunoglobulin like domains, class-5 semaphorins contain thrombospondin repeats and class-3 semaphorins contain a basic domain. Class-3 semaphorins are the only vertebrate semaphorins produced as secreted proteins while other vertebrate semaphorins are membrane anchored or trans-membrane proteins that can be further processed into soluble forms by proteolytic cleavage (Fig.

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Section: Semaphorins As Regulators Of Tumor Progressionmentioning

confidence: 99%

The role of the semaphorins in cancer

Neufeld

Mumblat

Smolkin

et al. 2016

Cell Adhesion & Migration

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“…Notably, Sema4A is greatly expressed in macrophages activated by inflammatory stimuli and recruited at the injured area in a cardiac ischemia/reperfusion model [91], suggesting its potential role in regulating pathological angiogenesis. Interestingly, Sema7A, shown to promote experimental angiogenesis [92], also enhances the production of several pro-inflammatory molecules (e.g., IL-8, Il-6 and IL-1β) in macrophages and increases theirs migration [93]. Sema4D secreted by TAMs enhances tumor angiogenesis and contributes to the maturation of tumor blood vessels.…”

Section: Semas Modulate the Function Of Tumor-associated Macrophages mentioning

confidence: 99%

The role of semaphorins and their receptors in vascular development and cancer

Giraudo

2013

Experimental Cell Research

103

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Summary Semaphorins (Semas) are a large family of traditional axon guidance molecules. Through interactions with their receptors, Plexins and Neuropilins, Semas play critical roles in a continuously growing list of diverse biological systems. In this review, we focus on their function in regulating vascular development. In addition, over the past few years a number of findings have shown the crucial role that Semas and their receptors play in the regulation of cancer progression and tumour angiogenesis. In particular, Semas control tumour progression by directly influencing the behavior of cancer cells or, indirectly, by modulating angiogenesis and the function of other cell types in the tumor microenvironment (i.e., inflammatory cells and fibroblasts). Some Semas can activate or inhibit tumor progression and angiogenesis, while others may have the opposite effect depending on specific post-translational modifications. Here we will also discuss the diverse biological effects of Semas and their receptor complexes on cancer progression as well as their impact on the tumor microenvironment.

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“…On the other hand, Sema7A has been shown to function as a regulator of the T-cell immune response by its effects on T-cell proliferation [16]. Notably, Sema7A has been demonstrated to have a clear effect on the migration processes of osteoblasts and osteoclasts in bone remodeling and a distinct role in tumor angiogenesis [17, 18]. Neovascularization, immunologic abnormality, and bone erosion all have crucial roles in the progression of RA [19, 20], suggesting that Sema7A may aggravate RA.…”

Section: Introductionmentioning

confidence: 99%

Semaphorin 7A as a potential immune regulator and promising therapeutic target in rheumatoid arthritis

Xie

Wang

2017

Arthritis Res Ther

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BackgroundSemaphorin 7A (Sema7A) is expressed by several different classes of lymphoid and myeloid cells and is a potent immunomodulator. We examined the role of Sema7A in modulating cellular immune responses and to provide experimental data validating the therapeutic potential of Sema7A in rheumatoid arthritis (RA).MethodsSoluble Sema7A (sSema7A) levels in the serum and synovial fluid from patients with RA or osteoarthritis, as well as cytokine secretions, were analyzed with an enzyme-linked immunosorbent assay. The cell surface levels and transcripts of Sema7A were evaluated in T cells and monocytes from patients with RA. The effect of Sema7A on the functions of primary T cells isolated from the peripheral blood of healthy donors was observed. Detection of the activation of the signal mediator focal adhesion kinase was performed by Western blotting. Shedding of sSema7A was evaluated in monocytes. The introduction of anti-Sema7A antibody to mice with collagen-induced arthritis (CIA) was observed in vivo.ResultsUpregulation of sSema7A levels in both the serum and synovial fluid of patients with RA was correlated with disease activity markers. sSema7A markedly increased Th1/Th17 cytokine secretion and induced evident upregulation of T-bet and retinoic acid receptor-related orphan nuclear receptor γt levels in T cells. Cell surface Sema7A was cleaved by a disintegrin and metalloprotease 17 (ADAM17) in monocytes. Interleukin-6 and tumor necrosis factor-α stimulated ADAM17 secretion in synovial macrophages. Blocking of β1-integrin abrogated the Sema7A-mediated cytokine secretion. Treatment with an anti-Sema7A antibody significantly attenuated CIA.ConclusionsThese findings indicate that Sema7A as a potent activator of T cells and monocytes in the immune response contributes to the inflammation and progression of RA, suggesting its therapeutic potential in the treatment of RA.

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Semaphorin 7A Promotes Angiogenesis in an Experimental Corneal Neovascularization Model

Cited by 33 publications

References 30 publications

The role of the semaphorins in cancer

The role of the semaphorins in cancer

The role of semaphorins and their receptors in vascular development and cancer

Semaphorin 7A as a potential immune regulator and promising therapeutic target in rheumatoid arthritis

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