Currently, there are very few diagnostic or therapeutic strategies targeted at controlling
tumor growth and progression towards
metastasis.
Uteroglobin (UG) is a naturally occurring, small, stable, secretory
protein that is normally expressed by most cells of epithelial origin but is known to be lost during the progression of prostate, lung, and
uterine cancers to invasive
malignancy.
Uteroglobin -/- knockout mice appear to be extremely
cancer prone. Both pharmacological and transgenic reconstitution of recombinant human UG (rhUG) to prostate, lung, and endometrial tumor cell lines markedly inhibits their invasiveness and antagonizes the neoplastic phenotype. In preliminary studies, rhUG inhibited angiogenesis in the ex vivo rat aorta model and showed antitumor activity against human prostate
tumor cells (PC-3) in the chick chorioallantoic membrane assay, reducing both
tumor volume and vascularity. A recent in vivo pilot study showed that twice daily dosing with rhUG resulted in a statistically significant increase in survival without evidence of toxicity in severe combined immunodeficient mice challenged with a PC-3 cell metastasizing
tumor. Thus, rhUG may slow the progression of
cancer by inhibiting both
tumor cell invasiveness and
tumor angiogenesis. It therefore holds the potential to serve as a new weapon in the arsenal of
cytostatic, antimetastatic, adjuvant treatment for
cancer. In this paper, we will briefly discuss the therapeutic potential of
uteroglobin-based strategies for managing
prostate cancer.