Cellular and Molecular Pathology Research Unit, Dept. Oral Pathology, Westmead Centre for Oral Health, Westmead Hospital, The University of Sydney, Westmead, NSW 2145, Australia.
Cytokine. 2013 Apr;62(1):48-51. doi: 10.1016/j.cyto.2013.02.028. Epub 2013 Mar 19.
We recently reported exchange of membrane and cytoplasm during contact co-culture between human Gingival Fibroblasts (h-GF) and SAOS-2 osteosarcoma cells, a process we termed 'cellular sipping' to reflect the manner in which cells become morphologically diverse through uptake of material from the opposing cell type, independent of genetic change. Cellular sipping is increased by Tumor Necrosis Factor-α (TNF-α), and we here show for the first time altered cytokine synthesis in contact co-culture supporting cellular sipping compared with co-culture where h-GF and SAOS-2 were separated in transwells. SAOS-2 had often undetectably low cytokine levels, while Interleukin-6 (IL-6), Granulocyte Colony Stimulating Factor (G-CSF) and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) were secreted primarily by TNF-α stimulated h-GF and basic Fibroblast Growth Factor (FGF) was prominent in h-GF lysates (p < 0.001). Contact co-cultures permitting cellular sipping had lower IL-6, G-CSF and GM-CSF levels, as well as higher lysate FGF levels compared with TNF-α treated h-GF alone (p < 0.05). The opposite was the case for co-cultures in transwells, with increased IL-6, G-CSF and GM-CSF levels (p < 0.03) and no clear difference in FGF. We thus demonstrate significant phenotypic change in cultures where cellular sipping occurs, potentially contributing to tumor inflammatory responses.
我们最近报道了人牙龈成纤维细胞（h-GF）和 SAOS-2 骨肉瘤细胞在接触共培养过程中细胞膜和细胞质的交换，我们将这一过程称为“细胞吸吮”，以反映细胞通过摄取来自相反细胞类型的物质而在形态上变得多样化的方式，而不依赖于遗传变化。肿瘤坏死因子-α（TNF-α）可增加细胞吸吮，我们首次显示与通过 Transwell 分离的共培养相比，支持细胞吸吮的接触共培养中细胞因子合成发生改变。SAOS-2 的细胞因子水平通常难以检测到，而白细胞介素 6（IL-6）、粒细胞集落刺激因子（G-CSF）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）主要由 TNF-α 刺激的 h-GF 分泌，碱性成纤维细胞生长因子（FGF）在 h-GF 裂解物中含量较高（p < 0.001）。与单独用 TNF-α 处理的 h-GF 相比，允许细胞吸吮的接触共培养物中的 IL-6、G-CSF 和 GM-CSF 水平较低，而裂解物中的 FGF 水平较高（p < 0.05）。Transwell 中的共培养则相反，IL-6、G-CSF 和 GM-CSF 水平升高（p < 0.03），而 FGF 没有明显差异。因此，我们在发生细胞吸吮的培养物中观察到显著的表型变化，这可能有助于肿瘤炎症反应。
