Substance p (sp) increases early onset adhesion of leukemia (Jurkat) and oral squamous cell carcinoma cell lines (OSCC) to endothelial cells (EC) via adhesion molecules: implication for metastasis.

Objectives: Metastasis is the leading cause of fatality in 90 % of cancer and approximately 60 % of patients will have metastasis at initial diagnosis. Understanding the adhesion of cancer cells as rate limiting steps in metastasis will improve the outcome of cancer. We hypothesized that cancer utilizes the inflammatory mediator SP to adhere to EC, in an acute phase, through inducing adhesion molecules expression.
Methods: We used Leukaemia cell line Jurkat (clone E6-1) and oral squamous cell carcinoma cell lines in different stages of the tumor (DOK, SCC25, CAL27, H157, and BICR22). Endothelial adhesion assay and fluorescence microscopy were used to quantify the adhesion of those cell lines to endothelial cells (HUV-EC-C) when treated with SP in an acute phase. Flow cytometry was used to measure the adhesion molecules (CD49, CD11, CD15s) in those cell lines treated with SP. Statistical analysis was done with ANOVA with CI of 95%.
Results: Treatment of Jurkat, H157, CAL27, DOK cell lines with SP significantly increased adhesion to EC in time dependent manner with a peak at 3 hours. SP treatment significantly increased the CD49 (VLA-4) in both Jurkat and CAL27. Using the NK-1R inhibitor and V-CAM monoclonal antibody significantly inhibited the adhesion to EC as well as the adhesion molecule expression compared with the TNF as a positive control.
Conclusions: Our results, albeit requiring further in-vivo validation, highlights potential role for SP in acute adhesion and extravasation of tumor cells through EC. The study has important implications for the development of novel strategies for “Metastasis Prevention”.