Stromal expression of connective tissue growth factor promotes angiogenesis and prostate cancer tumorigenesis.

Our previous studies have defined reactive stroma in human prostate cancer and have developed the differential reactive stroma (DRS) xenograft model to evaluate mechanisms of how reactive stroma promotes carcinoma tumorigenesis. Analysis of several normal human prostate stromal cell lines in the DRS model showed that some rapidly promoted LNCaP prostate carcinoma cell tumorigenesis and others had no effect. These differential effects were due, in part, to elevated angiogenesis and were transforming growth factor (TGF)-beta1 mediated.

Decreased stromal expression and increased epithelial expression of WFDC1/ps20 in prostate cancer is associated with reduced recurrence-free survival.

Background: WAP-type four disulfide core (WFDC1)/ps20 is a member of the whey acidic protein family, which includes several serine protease inhibitors. Expression of WFDC1/ps20 was previously demonstrated in the normal human prostate stromal compartment. To further current understanding of the role of WFDC1/ps20 in prostate cancer, altered expression of WFDC1/ps20 protein in prostate cancer was evaluated.

Promotion of angiogenesis by ps20 in the differential reactive stroma prostate cancer xenograft model.

Human prostate cancer is associated with a reactive stroma typified by an increase in the proportion of myofibroblast type cells and elevated synthesis of extracellular matrix proteins. Increased vascular density has been identified in the reactive stroma compartment adjacent to both precancerous and cancerous prostate lesions. The differential reactive stroma (DRS) prostate cancer xenograft model has been developed to investigate the role of reactive stroma in prostate cancer progression.

Inhibition of transforming growth factor-beta activity decreases angiogenesis in a human prostate cancer-reactive stroma xenograft model.

We have shown previously that reactive stroma promotes angiogenesis and growth of LNCaP human prostate tumors in the differential reactive stroma xenograft model. Regulators of reactive stroma are not known, but transforming growth factor (TGF)-beta1 is a likely candidate. Three-way differential reactive stroma tumors were generated in the presence of TGF-beta1 latency-associated peptide (LAP) or TGF-beta1 neutralizing antibody.

Stromal cells promote angiogenesis and growth of human prostate tumors in a differential reactive stroma (DRS) xenograft model.

Reactive stroma has been reported in many cancers, including breast, colon,and prostate. Although changes in stromal cell phenotype and extracellular matrix have been reported, specific mechanisms of how reactive stroma affects tumor progression are not understood. To address the role of stromal cells in differential regulation of tumor incidence, growth rate, and angiogenesis, LNCaP xenograft tumors were constructed in nude mice with five different human prostate stromal cell lines as well as GeneSwitch-3T3 cells engineered to express lacZ under mifepristone regulation.