Potential anti-metastatic properties of CTCE-9908 and L-kynurenine through the upregulation of cell-cell adhesion activity in a melanoma murine model

Melanoma, a highly metastatic form of skin cancer, is characterised by abnormal adhesion proteins expression leading to loss of epithelial integrity – a hallmark of cancer progression. Cell adhesion molecules are crucial in cancer progression and metastasis specifically in cancer cell interactions with the endothelium, which determine the metastatic spread to distant organs resulting in poor prognosis. Previous research showed that CTCE-9908, a chemokine inhibitor and L-kynurenine (L-kyn), a tryptophan metabolite induced cell death in vitro. This study investigated the combined effects of CTCE-9908 and L-kyn on tumour adhesion in vivo using a mouse model ( C57BL/6 mice transfected with B16-F10 melanoma). Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were used to assess key adhesion proteins namely, E-cadherin, focal adhesion kinase (FAK) and paxillin using in mice organs and tumours. Data showed a significant decrease in tumour volume in samples treated with the combination of CTCE-9908 and L-kyn when compared to the controls. An increase in FAK staining and a decrease in paxillin staining were observed in tumours treated with CTCE-9908 and CTCE/L-kyn. E-cadherin positive staining was seen in tumours treated with CTCE-9908 and CTCE/L-kyn. Results also showed a statistically significant increase in E-cadherin expression in serum samples treated with CTCE-9908 and CTCE/L-kyn. A statistically significant increase in FAK expression in serum samples treated with CTCE/L-kyn and L-kynurenine was observed when compared to negative controls. This study is the first to our knowledge to report on the anti-metastatic properties of CTCE-9908 and L-kyn in a melanoma mouse model by upregulating cell-cell adhesion activity. The National Research Foundation (NRF), Grant/Award Numbers: A1F4685, N1F580; The University Capacity Development Programme (UCDP), Grant/Award Numbers: A1D783, N1F120 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.