Role Of Substance P in Adhesion/Metastasis of Oral Cancer   

Objective: Metastasis is the leading cause of fatality in 90 % of cancer and approximately 60 % of patients will have metastasis at initial diagnosis. Furthermore, early detection of several types of cancer meant longer survival periods for patients and consequently higher incidence of recurrence. Understanding the mechanisms of metastasis, in particular extravastation and adhesion as rate limiting steps, will help in developing novel treatments and therefore improve outcome of cancer. We hypothesized that cancer utilizes the same method of leukocytes extravastation in the inflammation to disseminate to distant organ through substance P.
Method:

1- To examine the expression of binding legends of endothelial adhesion molecules in different oral cell lines and determine the effect of SP on this adhesion, using Immunocytochemistry.
2- To examine the adhesion of different oral cell lines to endothelial cells and determine the effect of SP on this adhesion.
3- To examine the effect of SP on the release of MMP in oral cell lines.
4- To develop in vivo 3D tumour/endothelial cell adhesion model.
Result: Treatment of oral cancer cell lines with 10µg of substance P for 30 minutes significantly increased staining for VLA-4 integrin both in the number of subjects and intensity. Whereas the treatment for 10 minutes increased the expression but it was not significant. Further confirmation of the results is being done with adhesion assay. Experiments were all done in duplicates and repeated with proper positive and negative ISO controls.
Conclusion: detecting the expression of endothelial adhesion molecules binding legends and the effect of substance P on this expression will provide an insight into the mechanism of oral cancer metastasis. The results can be integrated to develop a in vivo 3D tumour/endothelial cell adhesion model which can be ultimately provide the basis to develop a novel anti-metastatic therapy.