Monocyte-Induced Prostate Cancer Cell Invasion is Mediated by Chemokine ligand 2 and Nuclear Factor-?B Activity

Prostate cancer is the most common malignancy in American men and metastases are responsible for most prostate cancer mortality. Cancer metastasis is a multistep process in which the tumor microenvironment plays a role to promote aggressive cancer cell behavior. Inflammatory stimuli, especially involving macrophages and their accompanying cytokines are increasingly recognized factors that can promote cancer progression, but how this occurs is not fully understood.

Tumor-associated macrophages (TAM) and stromal cells may support tumor progression by promoting angiogenesis, immune suppression or direct effects on tumor cells. Co-cultures of breast cancer cells and monocytes have been shown to express cell-secreted factors which cause paracrine stimulation of tumor growth and progression. Several tumor specific cell-secreted factors have been identified that mediate interactions between cancer cells and monocytes. Paracrine stimulation of prostate cancer cells and monocytes has been hypothesized; however, studies are needed to determine precisely how prostate cancer cells and monocytes crosscommunicate to promote prostate cancer growth and progression.

Several cytokines and chemokines are produced by macrophages in the tumor microenvironment including IL-8, stromal-derived factor-1 (SDF-1) and CCL2. Prostate cancer cells express receptors for these and other chemokines and can respond to stimulation with growth, proliferation and metastasis. Interleukin 8 produced at high levels by prostate cancer cells can promote angiogenesis and androgen independent tumor growth. Prostate cancer cells that express CCL2 have been shown to cause monocyte and osteoclast recruitment with resulting cancer cell growth and survival.

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