Localization of a biotinylated cathepsin B oligonucleotide probe in human prostate including invasive cells and invasive edges by in situ hybridization.
The cysteine endopeptidase cathepsin B (CB) can degrade basement membrane (BM) proteins (such as laminin, type IV collagen, and fibronectin) at both acid and neutral pHs suggesting that CB has a role in tumor invasion and distant metastasis. The distribution and intensity of CB protein localization vary in normal prostate, benign prostatic hyperplasia (BPH), and neoplastic prostate. These considerations have led us to examine whether the distribution of CB localization in malignant and normal cells is due to storage or active synthesis of CB. In the present study, we examined the localization patterns of CB at the mRNA level in normal prostate, BPH, and well to moderately differentiated neoplastic prostate, focusing on invasive groups of cells and invasive edges of malignant tumors. We used a 25-base biotinylated oligonucleotide CB cDNA "sense" probe to localize CB message in prostate samples obtained from radical prostatectomies. We have determined that CB is actively synthesized by the epithelia of normal, hyperplastic, and neoplastic prostate including some invasive cells in the invasive edges. In both normal and BPH, CB mRNA was localized predominantly in acinar basal cells with some localization in cuboidal/columnar cells. In contrast, in neoplastic prostate, CB mRNA was localized predominantly in columnar cells and in groups of invasive cells and invasive edges. Thus, in malignant prostate the predominant cell types expressing CB differed from those of the normal prostate and BPH. Analysis of CB mRNA localizations indicated a heterogeneity in staining distribution in prostate cancer with some invasive groups of cells and invasive edges exhibiting CB mRNA and others exhibiting little or no reaction products.(ABSTRACT TRUNCATED AT 250 WORDS)
Sinha
A A
AA
Research Service, Veterans Affairs Medical Center, Minneapolis, MN 55417.
Gleason
D F
DF
Deleon
O F
OF
Wilson
M J
MJ
Sloane
B F
BF
D001483:Base Sequence; D002401:Cathepsin B / Q000032:analysis*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D011470:Prostatic Hyperplasia / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000737:chemistry*; D012333:RNA, Messenger / Q000032:analysis*
D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D002401:Cathepsin B