In Vitro and In Vivo Assessment of the Anti-Cancer Potential of Blocked PHSCN
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Plasma fibronectin is an extracellular matrix protein produced by the liver which aids cells in adhering to their substratum. In addition to this role, however, recent research has shown that in serum free medium, the presence of fibronectin can induce cancer cell invasion (Appendix, Figure 9). It was later demonstrated that the region of fibronectin containing modules 7-9 of its cell binding domain is responsible for invasion induction (Appendix, Figure 9). Ultimately, the sequence PHSRN on module 9 of fibronectin was determined to be specifically responsible for inducing cancer cell invasion (Appendix, Figure 10). Once the discovery that PHSRN can induce cancer cell invasion was made, it was inferred that an inhibitor of such a sequence could block such invasion and ultimately, inhibit carcinoma metastasis. Such an inhibitor (PHSCN) was then created and tested in both in vivo and in vitro studies. Previous research has shown that PHSCN does inhibit both metastasis and tumor growth. We continued to test the anti-cancer potential of this sequence but this time using a "blocked" version of the peptide. Blocking the peptide requires acetylating the sequence at its N-terminus and amidating it at its C-terminus. Such blocking allows the peptide to assume a more natural conformation and renders it resistant to exoproteases. The results of this study show that blocked PHSCN does inhibit both metastases and tumor growth at levels more pronounced than its unblocked counterpart.