UC San Diego

Interferon-gamma (IFNγ) has emerged as a significant player in cancer biology, influencing stem-like cell populations in various cancer contexts. While IFNγ is used as a treatment option for cancer patients based on its anti-tumorigenic effects it is seen to have off target effects where it promotes tumorigenesis paradoxically. It has been shown that IFNg exposure increases the expression of certain cancer stem cell (CSC) markers. However, the mechanism of this is not yet understood. This study addresses this critical gap in being able to understand the role of IFNg experience in the regulation of cancer. It is hypothesized that IFNg treatment of breast cancer and sarcoma cells would induce stem-like phenotypes, but the efficiency depends on whether STAT3 is activated by IFNg. So, if cells lacked STAT1, then IFNg should activate STAT3, and this could promote stemness, among other characteristics. This research has two areas of focus: in vitro and in vivo models of fibrosarcoma cell lines lacking or constituted with STAT1 and the effect of fludarabine (STAT1 inhibitor) on breast cancer cell lines. It is shown that IFNg exposure increases sphere formation and Sca1+/CD90- stem cell like marker expression in fibrosarcoma cells lacking STAT1 thereby potentially indicating that it is STAT3 behind these findings. In breast cancer models it was observed that fludarabine alone increase stem cell marker population as well as increases it even more synergistically with IFNg. These findings advance our understanding of the complex interplay of IFNg on the STAT1/STAT3 axis thereby effecting cancer stem cells in tumor biology.