# Osteoarthritis as a Systemic Disease Promoted Prostate Cancer In Vivo and In Vitro

## TL;DR

Osteoarthritis promotes prostate cancer growth and spread in mice through systemic factors, not direct effects of specific proteins.

## Contribution

This study is the first to show that osteoarthritis promotes prostate cancer progression in vivo and in vitro.

## Key findings

- OA media increased PCa cell proliferation and migration compared to controls.
- Mice with OA had higher tumor incidence and tumor weight correlated with OA severity.
- Tumors from OA mice showed increased Ki-67 expression, indicating higher cell proliferation.

## Abstract

Osteoarthritis (OA) is increasing worldwide, and previous work found that OA increases systemic cartilage oligomeric matrix protein (COMP), which has also been implicated in prostate cancer (PCa). As such, we sought to investigate whether OA augments PCa progression. Cellular proliferation and migration of RM1 murine PCa cells treated with interleukin (IL)-1α, COMP, IL-1α + COMP, or conditioned media from cartilage explants treated with IL-1α (representing OA media) and with inhibitors of COMP were assessed. A validated murine model was used for tumor growth and marker expression analysis. Both proliferation and migration were greater in PCa cells treated with OA media compared to controls (p < 0.001), which was not seen with direct application of the stimulants. Migration and proliferation were not negatively affected when OA media was mixed with downstream and COMP inhibitors compared to controls (p > 0.05 for all). Mice with OA developed tumors 100% of the time, whereas mice without OA only 83.4% (p = 0.478). Tumor weight correlated with OA severity (Pearson correlation = 0.813, p = 0.002). Moreover, tumors from mice with OA demonstrated increased Ki-67 expression compared to controls (mean 24.56% vs. 6.91%, p = 0.004) but no difference in CD31, PSMA, or COMP expression (p > 0.05). OA appears to promote prostate cancer in vitro and in vivo.