Possible Role of Semaphorin 3F, a Candidate Tumor Suppressor Gene at 3p21.3, in p53-Regulated Tumor Angiogenesis Suppression

Futamura, Manabu; Kamino, Hiroki; Miyamoto, Yuji; Kitamura, Noriaki; Nakamura, Yasuyuki; Ohnishi, Shiho; Masuda, Yoshiko; Arakawa, Hirofumi

doi:10.1158/0008-5472.can-06-2485

Cited by 86 publications

(83 citation statements)

References 47 publications

(55 reference statements)

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“…One can speculate that SEMA3D and SEMA3G could have similar properties and behave like anti-angiogenic proteins in gliomas. It can be noted that SEMA3F, now recognised as a tumour suppressor gene Kessler et al, 2004;Bielenberg et al, 2004;Kusy et al, 2005;Futamura et al, 2007) with antiangiogenic (Kessler et al, 2004;Futamura et al, 2007) and anti-metastatic properties (Bielenberg et al, 2004), did not show up as an important gene in our cohort of patients with gliomas. One explanation could be that SEMA3F protein is mostly present in nerve fibres and never detectable in glial cells and blood vessel in the adult human brain (Hirsch et al, 1999).…”

Section: Discussionmentioning

confidence: 65%

“…However, SEMA3B, like SEMA3F, is described as a tumour suppressor gene (Tomizawa et al, 2001;Tse et al, 2002). SEMA3F acts as a tumour suppressor gene by reducing angiogenesis and metastasis, probably through the inhibition of integrinmediated adhesion and VEGF expression Kessler et al, 2004;Bielenberg et al, 2004;Kusy et al, 2005;Futamura et al, 2007;Potiron et al, 2007). SEMA3B and SEMA3F are also direct p53 targets (Ochi et al, 2002;Futamura et al, 2007).…”

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confidence: 99%

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Semaphorin, neuropilin and VEGF expression in glial tumours: SEMA3G, a prognostic marker?

et al. 2008

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Gliomas are characterised by local infiltration, migration of tumour cells across long distances and sustained angiogenesis; therefore, proteins involved in these processes are most likely important. Such candidates are semaphorins involved in axon guidance and cell migration. In addition, semaphorins regulate tumour progression and angiogenesis. For cell signalling, class-4 semaphorins bind directly to plexins, whereas class-3 semaphorins require additional neuropilin (NRP) receptors that also bind VEGF 165 . The anti-angiogenic activity of class-3 semaphorins can be explained by competition with VEGF 165 for NRP binding. In this study, we analysed the expressions of seven semaphorins of class-3, SEMA4D, VEGF and the NRP1 and NRP2 receptors in 38 adult glial tumours. In these tumours, SEMA3B, SEMA3G and NRP2 expressions were related to prolonged survival. In addition, SEMA3D expression was reduced in high-grade as compared with low-grade gliomas. In contrast, VEGF correlated with higher grade and poor survival. Thus, our data suggest a function for a subset of class-3 semaphorins as inhibitors of tumour progression, and the prognostic value of the VEGF/SEMA3 balance in adult gliomas. Moreover, in multivariate analysis, SEMA3G was found to be the only significant prognostic marker.

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Section: Discussionmentioning

confidence: 65%

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confidence: 99%

Semaphorin, neuropilin and VEGF expression in glial tumours: SEMA3G, a prognostic marker?

et al. 2008

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“…Sema3F decreases tumor growth in a number of in vivo tumor models, and although Sema3F is capable of interacting with Nrp1, its higher-affinity interaction with Nrp2 appears to be required for its tumor-suppressive activity in many models [58][59][60]. Sema3F exerts a repulsive effect on breast cancer cells [61] and reduces the growth and metastatic activity of colorectal carcinoma cells by modifying integrin αvβ3 [62], suggesting that Sema3F affects tumor cells directly by controlling cell adhesion and migration.…”

Section: Sema3fmentioning

confidence: 99%

Semaphorin signaling in angiogenesis, lymphangiogenesis and cancer

2011

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Angiogenesis, the formation of new blood vessels from preexisting vasculature, is essential for many physiological processes, and aberrant angiogenesis contributes to some of the most prevalent human diseases, including cancer. Angiogenesis is controlled by delicate balance between pro-and anti-angiogenic signals. While pro-angiogenic signaling has been extensively investigated, how developmentally regulated, naturally occurring anti-angiogenic molecules prevent the excessive growth of vascular and lymphatic vessels is still poorly understood. In this review, we summarize the current knowledge on how semaphorins and their receptors, plexins and neuropilins, control normal and pathological angiogenesis, with an emphasis on semaphorin-regulated anti-angiogenic signaling circuitries in vascular and lymphatic endothelial cells. This emerging body of information may afford the opportunity to develop novel anti-angiogenic therapeutic strategies.

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“…Mice were sacrificed, and the resected tumors were weighed 30. The study was independently repeated twice.…”

Section: Methodsmentioning

confidence: 99%

Combination therapy with zoledronic acid and cetuximab effectively suppresses growth of colorectal cancer cells regardless of KRAS status

Kato

Futamura

Kanematsu

et al. 2015

Intl Journal of Cancer

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Targeted molecular therapy is an effective anticancer strategy. Anti‐EGFR monoclonal antibodies such as cetuximab (CTX) have been approved for the treatment of various malignancies, including colorectal cancer (CRC) with wild‐type KRAS. However, their efficacy in patients with KRAS mutations has not been established. Therefore, we investigated whether CTX treatment was effective as a single agent or in combination with zoledronic acid (ZOL) in human CRC cell lines with different KRAS status. CRC cell lines SW48 (wild‐type KRAS) and LS174T (mutant KRAS) were treated with ZOL, CTX and a combination of both drugs. Cytotoxicity was measured using the MTT assay. Changes in the levels of intracellular signaling proteins were evaluated using western blot analysis. Finally, we evaluated the efficacy of the combination treatment in an in vivo xenograft model. We observed that ZOL apparently inhibited growth in both cell lines, whereas CTX showed little effect. ZOL also increased the levels of unprenylated RAS. Combined ZOL and CTX treatment was synergistic in both cell lines and was associated with inhibition of the RAS‐MAPK and AKT‐mTOR signaling pathways. Furthermore, the combination treatment was more effective in suppressing the growth of xenografts derived from both SW48 and LS174T cells; this effect was associated with increased apoptosis. These results demonstrate that ZOL inhibits the growth of colon cancer cells regardless of KRAS status, and combination therapy using ZOL and CTX enhances this growth suppression. These findings suggest a novel strategy for the treatment of CRC independent of KRAS mutational status.

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Possible Role of Semaphorin 3F, a Candidate Tumor Suppressor Gene at 3p21.3, in p53-Regulated Tumor Angiogenesis Suppression

Cited by 86 publications

References 47 publications

Semaphorin, neuropilin and VEGF expression in glial tumours: SEMA3G, a prognostic marker?

Semaphorin, neuropilin and VEGF expression in glial tumours: SEMA3G, a prognostic marker?

Semaphorin signaling in angiogenesis, lymphangiogenesis and cancer

Combination therapy with zoledronic acid and cetuximab effectively suppresses growth of colorectal cancer cells regardless of KRAS status

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