Uteroglobin: a potential novel tumor suppressor and molecular therapeutic for prostate cancer.
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.
Patierno
Steven R
SR
Department of Pharmacology, The George Washington University Medical Center, Washington, DC 20037, USA. phmsrp@gwumc.edu
Manyak
Michael J
MJ
Fernandez
Patricia M
PM
Baker
Angela
A
Weeraratna
Ashani T
AT
Chou
David S
DS
Szlyk
Greg
G
Geib
K Shane
KS
Walsh
Christopher
C
Patteras
John
J
D000818:Animals; D001707:Biopsy, Needle; D002642:Chick Embryo; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010865:Pilot Projects; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D051381:Rats; D012680:Sensitivity and Specificity; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D014598:Uteroglobin / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use*
D014598:Uteroglobin