Role Of Tumor And Host Pin1 Status On Lewis Lung Carcinoma Growth

The peptidyl-proline isomerase, PIN1, is overexpressed in many cancers. Its depletion slowed the growth of human prostate tumors in athymic mice. Contrary to this, we found that PIN1 depletion in EMT6 murine mammary adenocarcinoma cells increased their growth in the mammary fat pad of wildtype BALB/c mice. Here we investigated the effect of tumor and of host PIN1 status on growth of another tumor in immunocompetent mice. We hypothesized that PIN1 depletion in Lewis Lung Carcinoma (LLC1) cells would increase growth in wildtype C57/BL6 mice, and that tumor growth would be further enhanced in pin1 -/- mice. Stable PIN1 knockdown or control LLC1 cells were produced by viral transduction. As with EMT6 cells, PIN1 knockdown in LLC1 cells decreased proliferation in vitro, compared to control (p<0.001). The effect of host PIN1 on tumor growth was then tested by subcutaneously injecting PIN1 knockdown or control LLC1 cells in pin1 wildtype or -/- mice. Like EMT6 tumors in BALB/c mice, PIN1 knockdown increased LLC1 tumor growth in wildtype mice (p<0.05). Interestingly, PIN1 knockdown tumors grew even faster in -/- than in wildtype mice (p<0.05), while growth of control tumors was unaffected by host PIN1 status. Thus, reductions in tumor and host PIN1 increased tumor growth. PIN1 may regulate host and tumor factors or the microenvironment to promote growth in immunocompetent mice.