Program
| MSE3c | |
|---|---|
| Afshin Beheshti | |
| Tufts University School of Medicine | |
| Title | The induction of DNA double-strand breaks in bystander stromal cells by cancer cells, a biological perspective |
| Abstract | We investigate in vitro and in vivo influences of tumor cells on neighboring stromal cells, as one aspect of multicellular effects during carcinogenesis. We study the constitutive level of DNA damage/repair, as indicated by standard g-H2AX and 53BP1 repair damage protein foci assays, in cells from tumors and neighboring stroma. We found that conditioned media from tumor cells produced an increase in genes related to DNA double-strand breaks (DSBs) in the stromal cells. In vivo studies also demonstrated a diffusive pattern of DNA DSBs in the stroma of the tumor. We demonstrate that cancer cells induce DSB and activate repair proteins in neighboring cells analogous to the radiation bystander effect, indicating that DNA damage is communicated among cells. This effect could indicate tumor subversion of the microenvironment to facilitate the breakdown of host barriers to tumor expansion and thus tumor progression. We develop a hybrid discrete continuous mathematical model of tumor growth within a stromal tissue environment. We show that certain tissue architectures can maintain the tumor in a space-restrained dormant stage. We simulate diffusion of stress-signals from the tumor to its microenvironment and induction of DNA DSBs in adjacent cells, which can with a certain frequency trigger cell death. We present simulation results that show how tumor-induced cell death can enable tumor progression and invasion. |
| Location | Woodward 3 |