These data suggest that the orthotopic injection of human prostate cancer cells into the nude mouse may provide a valuable model to study the biology and therapy of human prostate cancer.

BACKGROUND Several investigators have revealed that urokinase‐type plasminogen activator (uPA) and its receptor (uPAR) are overexpressed in serum as well as in tumor tissues in patients with various types of cancer. In this study, we examined whether the serum levels of uPA and uPAR could be used as predictors of the progression and prognosis of prostate cancer. METHODS Serum levels of uPA and uPAR in 54 healthy controls, 62 patients with benign prostatic hypertrophy (BPH), and 72 patients with prostate cancer were measured by a sandwich enzyme immunoassay. RESULTS The mean serum levels of uPA and uPAR in patients with prostate cancer were significantly higher than those in healthy controls and patients with BPH. Furthermore, the serum uPA and uPAR levels in prostate cancer patients with metastasis were significantly elevated compared with those in patients without metastasis. Among patients who underwent radical prostatectomy, the serum levels of uPA and uPAR in patients with pathologically organ‐confined disease were significantly lower than in those with advanced disease. The overall survival rate of prostate cancer patients with elevated serum levels of either uPA or uPAR, or of both, was significantly lower than that of patients with normal serum levels of uPA and uPAR. CONCLUSIONS The results of this study indicate that the elevation of serum levels of either uPA or uPAR, or of both, could be used as new predictors of progression and prognosis in patients with prostate cancer. Prostate 39:123–129, 1999. © 1999 Wiley‐Liss, Inc.

The relationship between expression of extracellular matrix degradative enzymes, angiogenesis and survival of multistage bladder cancer was determined. Expression of 3 extracellular matrix degradative enzymes (metalloproteinase-2, -9 and heparanase) and microvessel formation were examined in 40 resected bladder cancer specimens by immunohistostochemic staining, and then the association of the enzyme expression with angiogenesis and various stages of cancer was investigated. Heparanase protein expression in muscular invasive or lymph-node metastatic cancer was significantly higher than in superficial or nonmetastatic cancer, respectively (69% vs. 8%, p < 0.001, and 80% vs. 40%, p = 0.028, respectively). Interestingly, heparanase was expressed at much higher levels than matrix metalloproteinase-2 and -9. The mean microvessel count in cancers with heparanase expression was significantly higher than that in cancers without heparanase expression (32.3 +/- 18.2 vs. 5.5 +/- 6.1, p = 0.0008). The microvessel formation was not associated with the expression of matrix metalloproteinase-2 and -9. The cancer-specific and overall survival rates of patients with heparanase expression were significantly lower than those of patients without it (p = 0.0001 and p = 0.0008, respectively). Multivariate analysis showed that heparanase expression was a significantly independent prognostic factor for both cancer-specific (p = 0.0047) and overall survival (p = 0.0200). Our study suggested that heparanase plays important roles in invasion, angiogenesis and metastasis of bladder cancer, and thus, this molecule could be a new molecule to inhibit invasion, angiogenesis and metastasis of bladder cancer. Moreover, our results indicate that expression of heparanase could be a new prognostic factor of this disease.

By a combination of genome subtraction and comprehensive analysis of loss of heterozygosity based on mapping hemizygous deletions for a potential tumor-related locus, a minimum overlapping region of deletions at 9p24 the size of 165 kb was identified and found to harbor a new potential tumor suppressor gene for renal cell carcinoma, the Kank gene. Kank (for kidney ankyrin repeat-containing protein) contains four ankyrin repeats at its C terminus. Expression of the gene was suppressed in 6 of 8 or 6 of 10 cancer tissues examined by reverse transcription-PCR or Western blotting, respectively, and in several kidney tumor cell lines due to methylation at CpG sites in the gene. Epigenetic methylation or imprinting seemed to be the first hit, which was followed by a second hit of deletion, resulting in loss of function in many of these deletion cases. Expression of this gene in expression-negative HEK293 cells induced growth retardation at G 0 /G 1 as well as morphological changes.

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Our study implies that the expression of heparanase protein and mRNA is associated with bladder cancer invasion and metastasis, and heparanase may have a role in disease progression.

Our results indicate that endothelin receptor A expression may serve as a marker for and have an important role in prostate cancer progression.