We are pleased to announce a new publication from users of the Nanolive’s 3D Cell Explorer in the Medical University of Innsbruck, in Austria[1].

Epithelial mesenchymal crosstalk (EMC) describes the interaction between tumor stroma and its associated fibroblasts with epithelial cancer cells.

Increased invasiveness and mobility, radiochemotherapy resistance, and acquisition of a mesenchymal phenotype or stem-like properties are some of the results of EMC. Such effects are associated with generation of new tumors and metastasis. One of the factors involved in EMC is interleukin-6 (IL-6).

Understanding the mechanisms of EMC is necessary in order to prevent EMC-related effects. For this reason, Steinbichler, T.B. and colleagues analyzed the effect of IL-6-mediated EMC in head and neck cancer cells.

Samples of head and neck squamous cell carcinoma patients were used to perform immunohistochemical analysis of pan-cytokeratin, vimentin and alfa-SMA, as they are abundant components in ECM.

EMC-conditioned medium was produced from SCC-25 cells or Detroit 562 cells and human gingival fibroblasts. Flow cytometry was performed with the medium. Immunohistochemistry, protein isolation and MTT assays were also performed in SCC-25/Detroit 562 cells stimulated with EMC-conditioned medium and IL-6.

A SCC-25 cell line culture with EMC-conditioned medium or albumin and containing the half maximal inhibitory concentration (IC₅₀) of a well-known chemotherapeutic drug was used for a long-term observation (3 days) under the 3D Cell Explorer. Morphological properties of albumin-medium/drug and EMC-conditioned medium/drug were assessed by this mean.

The results showed that the mixed culture of SCC-25 cell line and HGF cells functioned as model of epithelial mesenchymal crosstalk, as high pan-cytokeratin and vimentin expression was found. Alfa-SMA, a maker of cancer associated fibroblasts, was also detected in the mixed culture.

Both this phenotype of this mixed culture and the biopsies of head and neck cancer patients were associated with radiochemotherapy resistance, migration and increased self-renewal.

The involvement of IL-6-STAT3 signaling pathway may explain the observed effect.

The 3D Cell Explorer allowed the experimenters to observe that the albumin-medium/drug sample cells died and released their adhesion from the culture dish. On the other hand, the ECM-conditioned medium/drug sample cells were alive and metabolically active. Mitochondria and lipid droplets were visualized, and a large, multinuclear morphology of that sample was described (Figure 1).

Their full publication is available here!

Figure 1. Long-term observation (3 days) under the 3D Cell Explorer. A,B) Albumin-medium drug sample cells died and released their adhesion from culture dish. C,D) ECM-conditioned medium/drug sample cells were alive and metabolically active. They also showed a large morphology. Some multinuclear cells, and several mitochondria and lipid droplets were also observed. Image from T. B. Steinbichler et al., “Pleiotropic Effects of Epithelial Mesenchymal Crosstalk on Head and Neck Cancer: EMT and beyond,” Cancer Microenviron., pp. 1–10, Jul. 2019.

[1]  T. B. Steinbichler et al., “Pleiotropic Effects of Epithelial Mesenchymal Crosstalk on Head and Neck Cancer: EMT and beyond,” Cancer Microenviron., pp. 1–10, Jul. 2019.

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