This overexpression occurs at the precursor stage (e.g. high-grade prostatic intraepithelial neoplasia or PIN) and persists throughout all stages of disease progression.
We are interested in understanding the inhibitory mechanism of metformin on tumor-associated inflammation in prostate cancer.<b>Experimental Design:</b> By using a transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model, <i>in vitro</i> macrophage migration assays, and patient samples, we examined the effect of metformin on tumor-associated inflammation during the initiation and after androgen deprivation therapy of prostate cancer.<b>Results:</b> Treating TRAMP mice with metformin delays prostate cancer progression from low-grade prostatic intraepithelial neoplasia to high-grade PIN, undifferentiated to well-differentiated, and PIN to adenocarcinoma with concurrent inhibition of inflammatory infiltration evidenced by reduced recruitment of macrophages.
Specific and strong immunostaining was found in a major proportion of cells in high-grade prostatic-intraepithelial-neoplasia (HG-PIN,12/17 patients), in most primary tumors (111/115), and in lymph node (11/15) and bone (12/15) metastases.