Project 4

1. Applicant

2. Topic

Role of ADAM-9 in tumor invasion and metastasis of malignant melanoma

3. Short summary

Tumor cell adhesion, mobility, proteolytic activities and cell receptors have important roles in cancer invasion. In the past years accumulated evidence has pointed to the contribution of ADAM-9 (A Disintegrin and Metalloprotease 9) to the development and spreading of various tumors such as prostate cancer and melanoma. However, the role for this protein in melanoma invasion and metastasis has been elusive. Using recombinant proteins and silencing approaches we have shown that this protein mediates cellular interactions between tumor and stromal cells. Furthermore, in vivo we could show that the expression of ADAM-9 in stromal fibroblasts may exert an anti-tumor activity whereas, its expression in melanoma cells may be necessary for cancer cells growth and penetration through basement membranes barriers. Surprisingly, several molecular alterations were detected in the absence of ADAM-9 during melanoma development in vivo, including up regulation of TNF, TIMP-1, and matrices. Thus, the scope of this project will be now to study the molecular mechanisms by which ADAM-9 regulates the expression of these proteins and in turn effect the development of melanoma. Furthermore, we aim to generate cell-specific tools to target ADAM-9 expression in vivo in melanoma but not stromal cells.

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