Immunohistochemical localization of cathepsin B in neoplastic human prostate

Abstract

Cathepsin B (CB) has been shown to degrade extracellular matrix (ECM) proteins, and has been reported to be involved in invasion and metastasis of several types of solid organ tumors in human and animals, but CB has not been studied in human prostate cancer (CAP). Our objective was to determine the CB protein immunostaining pattern in CAP and to correlate the immunostaining with the degree of malignancy as reflected in the Gleason grading system. We used two types of CB antibodies (namely, monospecific, polyclonal antibodies to human liver CB prepared in rabbits, and polyclonal antibody produced in sheep) to establish CB localization patterns in neoplastic prostate. Our analysis showed a heterogeneous CB immunostaining pattern in the neoplastic human prostate. CB immunostaining occurred in many, but not all, of the neoplastic columnar/cuboidal cells of acini and isolated cells, i.e., in small ragged glands and clusters (groups) of invasive cells in the prostatic stroma. We have shown that, in general, there was a positive correlation of the intensity of CB immunostaining with the Gleason histologic score (or Gleason grade sum) tumors, i.e., from the lowest scores through score 8, but many of the tumors with scores 9 and 10 showed little CB immunostaining. Our study indicated that the increased CB immunostaining in the Gleason grade sum 5-8 tumors may be associated with increased degradation of ECM, but not in 9 and 10 despite the fact that the latter tumors are more malignant clinically. In well-differentiated tumors, fewer CB immunostaining cells were present than the moderately-differentiated tumors. In other words, most of the stromal invasion of the prostatic ECM occurred in tumors of Gleason grade sums 5-8. We suggest that CB immunostaining might be a useful method to assess stromal invasion of prostatic carcinoma, especially in the higher grade tumors.

RNAi-mediated inhibition of cathepsin B and uPAR leads to decreased cell invasion, angiogenesis and tumor growth in gliomas

“…The results demonstrate that cathepsin B and uPAR play important roles in stimulating angiogenesis, suggesting a possible mechanism of action for the in vivo antitumor activity of pCU in the intracranial tumor model. Intense staining for cathepsin B is present in endothelial cells of neovessels but not in pre-existing microvasculature in prostate (Sinha et al, 1995) and human gliomas (Mikkelsen et al, 1995). Likewise, strong immunostaining of cathepsin B was observed in rat brain microvascular endothelial cells as they formed capillary tubes in vitro (Keppler et al, 1996).…”

Lysosomes in cell death

“…For example, increased expression and activity of cathepsin B and/or cathepsin D have been observed in breast (Castiglioni et al, 1994), colorectal (Campo et al, 1994;Meyer et al, 1997), gastric (Watanabe et al, 1989), lung (Sukoh et al, 1994), prostate (Sinha et al, 1995), and thyroid cancers (Shuja and Murnane, 1996), as well as in different brain tumors, including gliomas and meningiomas (Rempel et al, 1994;Levicar et al, 2003), and the magnitude of expression has often prognostic significance. Many authors have suggested that enhanced secretion of these proteases by exocytosis promotes cancer growth, invasion, and metastasis by promoting degradation of extracellular connective matrices and angiogenesis (Koblinski et al, 2000).…”

Human prostate tumor angiogenesis in nude mice: Metalloprotease and plasminogen activator activities during tumor growth and neovascularization of subcutaneously injected matrigel impregnated with human prostate tumor cells

“…Adjacent sections were examined for microvessels by immunohistochemistry for von Willebrand factor VIII (vWF) using a polyclonal rabbit anti-human vWF antibody (1:700 dilution, Dako Corp., Santa Barbara, CA) and subsequently treated with goat anti-rabbit antibodies avidin-biotin-peroxidase complex (Vectastain, Vector Labs, Burlingame, CA) as described previously (Sinha et al, , 1995a. The expression of prostate specific antigen (PSA) by the prostate tumor cells was determined immunohistochemically using a rabbit anti-human PSA (dilution of 1:800, Dako Corp.).…”