Salvo Elizabeth, Saraithong Prakaimuk, Curtin Jared G, Janal Malvin N, Ye Yi
Bluestone Center for Clinical Research, New York University College of Dentistry, New York, NY, 10010, USA.
DDS Program, New York University College of Dentistry, New York, NY, 10010, USA.
Heliyon. 2019 Feb 15;5(2):e01223. doi: 10.1016/j.heliyon.2019.e01223. eCollection 2019 Feb.
Pain associated with oral squamous cell carcinoma (oral SCC) decreases quality of life and survival. The interaction between cancer and the peripheral nerves is known to initiate and amplify pain and contribute to carcinogenesis. Schwann cells envelop peripheral nerves and are activated in response to neuronal damage. The contributions of Schwann cells to oral SCC progression and pain are unknown. Using a non-contact co-culture model, we demonstrate that Schwann cells (RSC-96) and oral SCC cells (HSC-3) reciprocally interact to promote proliferation, migration, and invasion. Schwann cell-oral SCC interaction leads to increased production of adenosine, which stimulates cell proliferation and migration of both cell types. The adenosine receptor A2B () is expressed on RSC-96 cells. We show that supernatant from the RSC-96 cells co-cultured with HSC-3 cells induces increased mechanical hypersensitivity in mice compared to supernatant from control RSC-96 cells. Treatment with the ADORA2B antagonist PSB603 significantly inhibits co-culture interactions - proliferation and migration, and co-culture supernatant induced mechanical hypersensitivity. RSC-96 cells co-cultured with HSC-3 cells secrete increased amounts of the pronociceptive mediator, interleukin-6 (IL-6), which can be reduced by adding PSB603 into the co-culture. Our data support a reciprocal interaction between oral SCC and Schwann cells mediated by adenosine with potential to promote oral SCC progression and pain via increased secretion of IL-6.
与口腔鳞状细胞癌（口腔鳞癌）相关的疼痛会降低生活质量和生存率。已知癌症与外周神经之间的相互作用会引发并加剧疼痛，并促进癌症发生。雪旺细胞包裹外周神经，并在神经元损伤时被激活。雪旺细胞对口腔鳞癌进展和疼痛的作用尚不清楚。我们使用非接触共培养模型证明，雪旺细胞（RSC-96）和口腔鳞癌细胞（HSC-3）相互作用以促进增殖、迁移和侵袭。雪旺细胞与口腔鳞癌的相互作用导致腺苷生成增加，腺苷可刺激两种细胞类型的增殖和迁移。腺苷受体A2B在RSC-96细胞上表达。我们发现，与对照RSC-96细胞的上清液相比，与HSC-3细胞共培养的RSC-96细胞的上清液会使小鼠的机械性超敏反应增强。用ADORA2B拮抗剂PSB603处理可显著抑制共培养相互作用——增殖和迁移，以及共培养上清液诱导的机械性超敏反应。与HSC-3细胞共培养的RSC-96细胞分泌更多的伤害感受性介质白细胞介素-6（IL-6），在共培养中加入PSB603可减少IL-6的分泌。我们的数据支持口腔鳞癌与雪旺细胞之间由腺苷介导的相互作用，这种相互作用可能通过增加IL-6的分泌来促进口腔鳞癌的进展和疼痛。
