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.
