Elucidating the role of cancer-induced Schwann cell reprogramming in tumour progression

Sammanfattning

Background The emerging field of cancer neuroscience has demonstrated that reciprocal signalling between neurons and cancer cells influences key aspects of disease progression, including tumour cell proliferation, invasion, and therapy resistance. Neurons are supported by Schwann cells (SCs), glial cells with a key role in nerve repair after injury. However, the role of SCs in the microenvironment of solid tumours remains to be explored. Aims The aims of this project were to establish a co-culture model to evaluate interactions between SCs and ductal carcinoma in situ (DCIS) cells, and to measure the extent of SC activation in DCIS lesions using spatial proteomics in nerve-irrigated tissue. Materials & Methods Direct and indirect co-cultures of DCIS cells with hTERT-immortalized human SCs and SH-SY5Y neuronal-like cells were established and characterized using cell proliferation-, clonogenic-, and transwell migration assays. A “nerve damage” panel was evaluated on the Akoya Phenoimager system using multiplex immunofluorescence stainings with Opal dyes. Results A 1.5-fold decrease in colony formation was detected in neuronal-like cells growing in DCIS cells conditioned media (p < 0.006), as well as a 3-fold decrease in DCIS cells growth in indirect co-culture with neuronal cells (p < 0.0005). To further study changes in SCs in the presence of injured neurons and to decipher their effects in breast cancer (BC) at the whole-tissue level, a panel of markers for multiplex immunofluorescence (mIF) analysis was developed. Conclusions We have established a strategy to reveal interactions between SCs and BC cells in nerve-irrigated tumours. This present study may generate a spatial pattern linking nerve damage and SC activation to programs that predict progression risk.