Jiao Cao1, Chen Zhang1, Ting Chen1, Rong Tian1, Shuhong Sun1, Xianshui Yu1, Chunying Xiao1, Gang Wang1, Yufeng Liu1, Meng Fu2, Wei Li3. 1. Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi'an 710032, Shaanxi, China. 2. Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi'an 710032, Shaanxi, China. Electronic address: fumeng@fmmu.edu.cn. 3. Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi'an 710032, Shaanxi, China. Electronic address: liwei1@fmmu.edu.cn.
Abstract
BACKGROUND OBJECTIVES: Semaphorin 4D (Sema4D) and its receptor, Plexin-B1, are involved in the pathogenesis of squamous cell carcinoma (SCC) by mediating angiogenesis or perineural invasion through the interaction between Sema4D expression on SCC cells and Plexin-B1 expression on endothelial cells or nerves. Plexin-B1 was also recently found to be expressed on SCC cells. Plexin-B1 expression on several types of tumor cells could mediate various, and occasionally opposing, effects, including tumor cell survival, proliferation, angiogenesis, invasion, and metastasis. However, whether Sema4D exerts paracrine or autocrine effects on SCC via Plexin-B1 remains unclear. OBJECTIVES: The aim of this study is to explore the effects of Sema4D/Plexin-B1 interaction on SCC via Plexin-B1 expressed on the tumor cells. METHODS: In the present study, we detected the expression of Plexin-B1 and Sema4D in cutaneous SCC (cSCC) tissues and in the cSCC cell line A431 and analyzed the effects of the Sema4D/Plexin-B1 interaction on cSCC cell proliferation, migration, and invasion, as well as on the signaling pathway downstream of Plexin-B1. RESULTS: We observed significantly increased Plexin-B1 and Sema4D expression in keratinocytes in cSCC lesions and in A431 cells compared with that in normal skin tissue and in non-malignant keratinocytes. Plexin-B1 silencing reduced the growth, proliferation, migration, and invasion of A431 cells and inhibited the phosphorylation of Akt and extracellular signal-regulated protein kinase (Erk). Soluble recombinant Sema4D promoted the growth, proliferation, migration, and invasion of A431 cells; Akt and Erk phosphorylation is also involved in these processes with a Plexin-B1 dependent manner. CONCLUSION: Plexin-B1 induces cSCC cell proliferation, migration, and invasion by interacting with Sema4D. Plexin-B1 might serve as a useful biomarker and/or as a novel therapeutic target for cSCC.
BACKGROUND OBJECTIVES:Semaphorin 4D (Sema4D) and its receptor, Plexin-B1, are involved in the pathogenesis of squamous cell carcinoma (SCC) by mediating angiogenesis or perineural invasion through the interaction between Sema4D expression on SCC cells and Plexin-B1 expression on endothelial cells or nerves. Plexin-B1 was also recently found to be expressed on SCC cells. Plexin-B1 expression on several types of tumor cells could mediate various, and occasionally opposing, effects, including tumor cell survival, proliferation, angiogenesis, invasion, and metastasis. However, whether Sema4D exerts paracrine or autocrine effects on SCC via Plexin-B1 remains unclear. OBJECTIVES: The aim of this study is to explore the effects of Sema4D/Plexin-B1 interaction on SCC via Plexin-B1 expressed on the tumor cells. METHODS: In the present study, we detected the expression of Plexin-B1 and Sema4D in cutaneous SCC (cSCC) tissues and in the cSCC cell line A431 and analyzed the effects of the Sema4D/Plexin-B1 interaction on cSCC cell proliferation, migration, and invasion, as well as on the signaling pathway downstream of Plexin-B1. RESULTS: We observed significantly increased Plexin-B1 and Sema4D expression in keratinocytes in cSCC lesions and in A431 cells compared with that in normal skin tissue and in non-malignant keratinocytes. Plexin-B1 silencing reduced the growth, proliferation, migration, and invasion of A431 cells and inhibited the phosphorylation of Akt and extracellular signal-regulated protein kinase (Erk). Soluble recombinant Sema4D promoted the growth, proliferation, migration, and invasion of A431 cells; Akt and Erk phosphorylation is also involved in these processes with a Plexin-B1 dependent manner. CONCLUSION:Plexin-B1 induces cSCC cell proliferation, migration, and invasion by interacting with Sema4D. Plexin-B1 might serve as a useful biomarker and/or as a novel therapeutic target for cSCC.
Authors: Konstantinos Lontos; Juraj Adamik; Anastasia Tsagianni; Deborah L Galson; John M Chirgwin; Attaya Suvannasankha Journal: Front Endocrinol (Lausanne) Date: 2018-06-19 Impact factor: 5.555
Authors: Rania H Younis; Ioana Ghita; Manar Elnaggar; Risa Chaisuparat; Vasileios Ionas Theofilou; Donita Dyalram; Robert A Ord; Eduardo Davila; Luke J Tallon; John C Papadimitriou; Tonya J Webb; Søren M Bentzen; Joshua E Lubek Journal: Front Immunol Date: 2021-03-11 Impact factor: 7.561