Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P11684 (Uteroglobin)
 114 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uteroglobin (UG) is a potent immunomodulatory and antiinflammatory secretory protein with high levels detected in human prostate tissue. We used three human prostate cancer cell lines (DU-145, PC3-M, and LNCaP) to test the hypothesis that UG may modulate invasiveness of prostatic carcinoma cells in the Boyden chamber assay for invasion through a reconstituted basement membrane preparation. Fibroblast-conditioned medium was used as the chemoattractant. The most invasive cell line was DU-145, followed by PC3-M, whereas the androgen-dependent LNCaP cell line exhibited extremely low invasive potential. Pretreatment of DU-145 and PC3-M cells for 24 h with 0.01, 0.1, or 1.0 microM recombinant UG had no effect on basal invasiveness but inhibited fibroblast-conditioned medium-stimulated invasion in a dose-dependent manner, reaching up to 60.2 and 87.9% inhibition of DU-145 and PC3-M, respectively. UG had no effect on either cell-reconstituted basement membrane adhesion or simple chemotaxis in the absence of reconstituted basement membrane. UG also strongly inhibited the biphasic release of [14C]-labeled arachidonic acid from fibroblast-conditioned medium-stimulated DU-145 cells. These results suggest that UG may modulate prostate tumor cell invasiveness and that the mechanism may include inhibition of the arachidonic acid signal cascade.
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PMID:Recombinant human uteroglobin inhibits the in vitro invasiveness of human metastatic prostate tumor cells and the release of arachidonic acid stimulated by fibroblast-conditioned medium. 803 85

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.
Clin Prostate Cancer 2002 Sep
PMID:Uteroglobin: a potential novel tumor suppressor and molecular therapeutic for prostate cancer. 1504 3