Circulating hTERT (human telomerase) mRNA in Exosomes Derived from T-Cell Leukemia Cells Promotes the Aggressiveness of Microenvironment Related Primary Fibroblasts

The importance of the cancer microenvironment to the establishment and aggressiveness of tumors has been well established. One of the mediators of the intensive crosstalk between cancer microenvironment and the tumor mass are exosomes. These are small vesicles (30-100 nm in size) secreted from all types of cells into the body fluids and cell surroundings. They contain a variety of proteins, lipids and amino acids including DNA, RNA and micro RNAs. In the present study we explored whether hTERT, the mRNA transcript of human telomerase is secreted from cancer cells via exosomes. We present data which describes the secretion of hTERT transcript into exosomes derived from Jurkat (T-cell leukemia) cells. We show that exosomal hTERT is transferred to recipient fibroblasts where it is translated to a fully active enzyme. Upon translation, telomerase is able to change the phenotype of these primary non-telomerase expressing fibroblasts by increasing the primary fibroblasts` proliferation and protecting them from DNA damage imposed on these cells. These results suggest that the transfer of hTERT from the tumor to the surrounding microenvironment contributes to the capability of the cancer microenvironment to become more tumors supportive by transforming fibroblast cells into cancer associated fibroblasts. Overall, understanding of these mechanisms may have a strong impact on deciphering metastases formation.