KLK4 Induces Anti-Tumor Effects in Human Xenograft Mouse Models of Orthotopic and Metastatic Prostate Cancer.

Simple Summary The serine protease kallikrein-related peptidase 4 (KLK4) has been reported to potentially play a role in the progression of prostate cancer and other cancer types. However, most of these reports have been limited to in vitro studies. In vivo cancer models offer greater complexity to mimic the characteristics of cancer growth and metastasis in humans. In this study, we used in vivo models of prostate cancer and demonstrated that KLK4 can strongly inhibit the growth of primary prostate tumors as well as bone metastases. To our knowledge, this is the first report of an anti-tumor effect of KLK4 in prostate cancer in vivo. Recent reports have suggested the role of kallikrein-related peptidase 4 (KLK4) to be that of remodeling the tumor microenvironment in many cancers, including prostate cancer. Notably, these studies have suggested a pro-tumorigenic role for KLK4, especially in prostate cancer. However, these have been primarily in vitro studies, with limited in vivo studies performed to date. Herein, we employed an orthotopic inoculation xenograft model to mimic the growth of primary tumors, and an intracardiac injection to induce metastatic dissemination to determine the in vivo tumorigenic effects of KLK4 overexpressed in PC3 prostate cancer cells. Notably, we found that these KLK4-expressing cells gave rise to smaller localized tumors and decreased metastases than the parent PC-3 cells. To our knowledge, this is the first report of an anti-tumorigenic effect of KLK4, particularly in prostate cancer. These findings also provide a cautionary tale of the need for in vivo analyses to substantiate in vitro experimental data.