Abstract
The treatment of cancer such as oligonucleotides or peptides requires efficient delivery systems. A novel peptide, TMTP1, previously derived and identified in our laboratory showed remarkable ability to target highly metastatic tumors both in vitro and in vivo, even at the early stage of occult metastasis foci. TMTP1 moderately inhibited tumor cell viability, although not enough to deem it an efficient killer of tumor cells. In this study, we sought to enhance the anti-tumor activity of TMTP1. To do this, we fused it to an antimicrobial peptide, D(KLAKLAK)2, and termed the resulting peptide TMTP1-DKK. We found that TMTP1-DKK could trigger rapid apoptosis in human prostate and gastric cancer cells through both the mitochondrial-induced apoptosis pathway and the death receptor pathway. Furthermore, direct injection of TMTP1-DKK into mice with prostate and gastric xenograft cancers resulted in reduction of tumor volumes and a significant delay in tumor progression and metastasis in vivo. These results suggest that TMTP1-DKK may serve as a powerful therapeutic agent for metastatic tumors.
Highlights
The majority of mortality associated with cancer is due to metastasis of the original tumor cells to sites distant from the initial or primary tumor
We have previously shown that TMTP1 binds to metastatic tumor cells [11]
We examined the binding of Fluorescein isothiocyanate (FITC)-conjugated TMTP1-DKK to several cancer cell lines and normal cells in vitro and in vivo
Summary
The majority of mortality associated with cancer is due to metastasis of the original tumor cells to sites distant from the initial or primary tumor. Gastric cancer remains one of the most frequent neoplasms, causing 12% of all cancer-related deaths each year [1,2,3]. The hope is that by targeting specific alterations in cancer cells at the early stage of metastasis, therapies can be developed to be more effective in killing tumor cells in situ and metastasis foci, while less harmful to normal cells. As a result, these innovative therapies would make a major positive impact on the survival and quality of life of cancer patients
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