Schwann Cells Induce Phenotypic Changes in Oral Cancer Cells

Abstract

Head and neck cancer (HNC) is the seventh most common cancer worldwide, the majority being oral squamous cell carcinoma. Despite advances in cancer diagnosis and treatment, the survival rate of patients with HNC remains stagnant. The cancer-nerve interaction has been recognized as an important driver of cancer progression. Schwann cells, a type of peripheral glia, have been implicated in promoting cancer cell growth, migration, dispersion, and invasion into the nerve in many cancers. Here, it is demonstrated that the presence of Schwann cells makes oral cancer cells more aggressive by promoting their proliferation, extracellular matrix breakdown, and altering cell metabolism. Furthermore, oral cancer cells became larger, more circular, with more projections and nuclei following co-culturing with Schwann cells. RNA-sequencing analysis in oral cancer cells following exposure to Schwann cells shows corresponding changes in genes involved in the hallmarks of cancer and cell metabolism; the enriched KEGG pathways are spliceosome, RNA transport, cell cycle, axon guidance, signaling pathways regulating pluripotency of stem cells, cAMP signaling, WNT signaling, proteoglycans in cancer and PI3K-Akt signaling. Taken together, these results suggest a significant role for Schwann cells in facilitating oral cancer progression, highlighting their potential as a target to treat oral cancer progression.

Schwann cells in the normal and pathological lung microenvironment

“…Our recognition of the relevance of SC activity and lung cancer is still in its infancy although the important role of SCs in other cancer types has already been demonstrated ( Deborde and Wong, 2017 ; Martyn et al, 2019 ; Shurin et al, 2021 ; Deborde and Wong, 2022 ; Yurteri et al, 2022 ). Analysis of SC biology in prostate, pancreatic, cervical, oral, colon tumors, melanoma, and other cancer types revealed their involvement in perineural invasion, cancer pain, and tumor cell proliferation, dispersion, invasion, and metastasizing ( Demir et al, 2014 ; Deborde et al, 2016 ; Shan et al, 2016 ; Shurin et al, 2019 ; Huang et al, 2020 ; Salvo et al, 2021 ; Santi et al, 2022 ). It was also shown that the proregenerative state of tumor-activated SCs is important for the stimulation of tumor development, progression, and metastasis ( Shurin et al, 2020 ; Pascual et al, 2021 ; Deborde and Wong, 2022 ).…”