ArticleOncoTargets and therapy2016
The role of semaphorin 4D as a potential biomarker for antiangiogenic therapy in colorectal cancer.
Article in OncoTargets and therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Semaphorin 4D (CD100) expression as a predictor for the response to induction therapy in pediatric patients with B-acute lymphoblastic leukemia.European journal of pediatrics · 2026Article
- Associations of SEMA7A, SEMA4D, ADAMTS10, and ADAM8 with KRAS, NRAS, BRAF, PIK3CA, and AKT Gene Mutations, Microsatellite Instability Status, and Cytokine Expression in Colorectal Cancer Tissue.Current issues in molecular biology · 2024Article
- The long non-coding RNA NEAT1 promotes the progression of human ovarian cancer through targeting miR-214-3p and regulating angiogenesis.Journal of ovarian research · 2023Article
- Semaphorin 4D Induces Vasculogenic Differentiation of Dental Pulp Stem Cells.Dentistry journal · 2023Article
- Leptin and melatonin's effects on OVX rodents' bone metabolism.Frontiers in endocrinology · 2023Article
- Present Status, Challenges, and Prospects of Dihydromyricetin in the Battle against Cancer.Cancers · 2022Review
- Cytokine profiling in plasma distinguishes the histological inflammatory subtype of head and neck squamous cell carcinoma and a novel regulatory role of osteopontin.Frontiers in oral health · 2022Article
- Semaphorin 4D is a potential biomarker in pediatric leukemia and promotes leukemogenesis by activating PI3K/AKT and ERK signaling pathways.Oncology reports · 2021Article
- Review
- CPEB1 Expression Correlates with Severity of Posttraumatic Ankle Osteoarthritis and Aggravates Catabolic Effect of IL-1β on Chondrocytes.Inflammation · 2019Article
- The Role of Semaphorin 4D in Bone Remodeling and Cancer Metastasis.Frontiers in endocrinology · 2018Review
- The role of semaphorin 4D in tumor development and angiogenesis in human breast cancer.OncoTargets and therapy · 2016Article
- Partial Oxygen Pressure Affects the Expression of Prognostic Biomarkers HIF-1 Alpha, Ki67, and CK20 in the Microenvironment of Colorectal Cancer Tissue.Oxidative medicine and cellular longevity · 2016Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSemaphorin 4D (Sema4D) belongs to the class IV semaphorins, and accumulating evidence has indicated that its elevated level may be one strategy by which tumors evade current anti-angiogenic therapies. The biological roles of Sema4D in colorectal cancer (CRC), however, remain largely undefined. This study was designed to investigate the effects of Sema4D on tumor angiogenesis and growth in CRC, especially in different vascular endothelial growth factor (VEGF) backgrounds.
methodsThe expression of Sema4D in human CRC was evaluated by immunohistochemical analysis of tumors and their matching normal control tissues. The expression level of Sema4D and VEGF was investigated in different CRC cell lines. To evaluate the contributions of Sema4D to tumor-induced angiogenesis, two CRC cell lines with opposite VEGF backgrounds were infected with lentiviruses expressing Sema4D or Sema4D short hairpin RNA, followed by in vitro migration and in vivo tumor angiogenic assays.
resultsImmunohistochemical analysis of human CRC revealed high levels of Sema4D in a cell surface pattern. In all, 84.85% of CRC samples analyzed exhibited moderate to strong Sema4D expression. The positive ratios of Sema4D staining for well, moderately, and poorly differentiated cancers were 71.43%, 96.67%, and 77.27%, respectively. Sema4D is highly expressed in five different CRC cell lines, while VEGF expression level varies among these cell lines. HCT-116 showed the lowest VEGF level, while Caco-2 showed the maximum VEGF level. In vitro migration results show that regardless of cell type and VEGF background, Sema4D showed an enhanced in vitro proangiogenic effect to induce the migration of human umbilical vein endothelial cells. Finally, in vivo tumor angiogenic assays demonstrated that Sema4D alone can elicit a significant angiogenic response to promote tumor growth independently of VEGF.
conclusionTargeting Sema4D might serve as a parallel option for antiangiogenic therapy for CRC, particularly when traditional anti-VEGF therapies fail or tumors develop resistance to strategies targeting a single angiogenic signaling pathway.
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