## 4 Discussion
The idea of CAP selectivity for cancer cells has been debated recently and a selective CAP effect on tumour cells has been ascribed to divergent metabolic features, anti-oxidative capacity or erroneous signalling processes [24; 25; 44; 45]. In addition to cytotoxic events, the cells motility also was investigated. To preclude a risk, HaCaT and HNO97 cells were tested for their ability to move into a scratch. In this model, CAP treatment significantly decreased cell motility in squamous cell carcinoma cells only but not in non-malignant keratinocytes. Protein expression profiles support this finding by identifying reduced expression of several proteins related to cytoskeleton rearrangement, motility and cell migration. Cell motility as well as cell-cell-adhesion are both closely related to the expression of E-cadherin among other adhesion molecules. Previous research showed that the expression of E-cadherin negatively correlates with the progression of oral squamous cell carcinoma and dedifferentiation [46]. Interestingly, elevated E-cadherin and EGFR expression level were earlier detected after CAP treatment in HaCaT keratinocytes [47] but not in HNO97 cells. Notably, the expression of angio-associated migratory cell protein (AAMP) also correlated with the migratory activity in several cell types, including smooth muscle cells and endothelial cells [48]. The expression of AAMP was reduced after CAP treatment in HNO97, whereas its expression slightly increased in HaCaT cells depending on the treatment intensity and time point [49]. We also observed that AAMP was secreted into the extracellular compartment and acts upon neighbouring cells, potentially contributing to remote effects of CAP. Interestingly, for non-malignant murine fibroblasts a change in integrin expression concomitant with reduced motility after CAP exposure was reported earlier [50]. Moreover, we found that also SK-MEL-147 human melanoma cells displayed significantly decreased cell motility when subjected to CAP-treated medium [51]. This effect was correlated with alterations in the cytoskeleton, such as actin fibre rearrangement, and hence agrees well with alterations in non-melanoma skin cancer cells. Regarding redox signalling events our results are in accordance with [PERSON] et al., who described unaltered protein levels of peroxiredoxin 1 and 2 after CAP exposure [52]. Moreover, our results illustrate the high complexity and heterogeneity of tumour tissue consisting of extracellular matrix, immune cells and epithelial cells. This led us to investigate extracellular cytokines after CAP exposure that function as mediators. Our results merely detected four immunomodulatory cytokines with different concentrations in healthy versus tumour tissue. Especially IL10 has been detected at higher levels in squamous cell carcinoma by others [53] and is in accordance with our finding. Considering the central role of INF\(\gamma\) in keratinocyte apoptosis and TNF\(\alpha\)'s potential to increase this effect, it is noticeable that our approach revealed an increased concentration of INF\(\gamma\) and TNF\(\alpha\) after CAP treatment in tumour tissue [54]. This is in good agreement with detected elevated cytochrome c levels after CAP treatment. Effects mediated by second messenger like the AAMP protein or the interleukins and cellular signalling in response to CAP application remain largely elusive but require more attention in future approaches. Intriguingly variations between HaCaT keratinocytes and HNO97 squamous cell carcinoma cells were rather minor in our 2D cell culture approach whereas patient derived tissue revealed very differential responses towards CAP treatment. This finding highlights the need to employ clinically relevant model systems for further preclinical investigations of CAP.