Abstract 387: Prostate cancer cell invasion is stimulated by cross communication with human monocyte-lineage cells

Tumor-associated macrophages (TAMs) produce factors that may stimulate tumor growth, angiogenesis and progression. In this study, co-cultures with monocyte-derived THP-1, U-937 cells or normal peripheral blood monocytes stimulated PC-3, DU145 and LNCaP prostate cancer cell basement membrane invasion. This study investigated the interactions between monocytes and prostate cancer cells leading to increased cancer cell invasion. The PC-3 prostate cancer cells expressed high levels of IL-6 and IL-8, at similar levels to co-cultures with human U-937 monocyte-derived cells. However, the co-culture supernatants showed increased MCP-1 levels, up to 5 ng/mL, compared with prostate cancer cells cultured alone with MCP-1 less than 10 pg/mL. During the co-cultures, MCP-1 was first detected at 8 hours and increased over 3 days. Co-culture of U-937 or THP-1 monocytes with either DU145 or LNCaP cells also increased MCP-1 expression significantly above cancer cell or monocyte cultures alone. When cultured separately, the monocyte-lineage cells produced more MCP-1 than the cancer cells; however, MCP-1 expression increased more than 10-fold in the co-cultured prostate cancer cells. Addition of purified MCP-1 and IL-8 stimulated prostate cancer cell invasion to levels similar to the co-cultures. Further, addition of anti-MCP-1 neutralizing antibodies inhibited prostate cancer cell invasion when compared with control antibodies. Co-culture with U-937 cells also stimulated NF-κB DNA binding activity in the prostate cancer cells. Transfection of the prostate cancer cells with dominant negative IκBα or treatment of the co-cultures with Bay11-7082 or Lacticystin inhibited NF-κB DNA binding and prostate cancer cell invasion. These experiments demonstrate that human monocyte-derived cells can cross-communicate with prostate cancer cells leading to increased cancer cell invasion. These studies have potential to identify treatments to target MCP-1 and NF-κB activity to inhibit monocyte-induced cancer cell invasion and progression. Support by Northwestern University Prostate S.P.O.R.E. P50CA90386 and CDMRP DAMD-17-02-1-0162Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 387. doi:10.1158/1538-7445.AM2011-387

Duke Scholars

Author Susan Crawford Pathology