Intermediate filament expression and the progression of prostatic cancer as studied in the dunning R‐3327 rat prostatic carcinoma system
Authors: Ramaekers Frans C. S. , Verhagen Anja P. M. , Isaacs John T. , Feitz Wouter F. J. , Moesker Olof , Schaart Gert , Schalken Jack A. , Vooijs G. Peter 
Published: February 2007

To evaluate if there is any consistent relationship between the expression of intermediate filament proteins (IFP), particularly keratins, and the degree of malignancy of prostatic cancer cells, a series of nine Dunning rat prostatic cancer sublines that span the entire spectrum of progression of prostatic cancer were studied immunocytochemically by the use of a variety of antibodies specific for keratins, vimentin, or desmin. For the keratin studies, monoclonal antibodies with either a general reactivity to several keratins or highly specific for either luminal or basal epithelial cells of the normal rat prostate were used.

By use of an antibody specific for luminal cell keratin 18, the luminal tumor cells of the well‐differentiated, slow‐growing H and HI‐S sublines were positively stained. In most of the sublines with a more advanced state of progression (i.e., the moderately differentiated, moderately fast growing HI‐M; the poorly differentiated, faster growing HI‐F; and the anaplastic, very fast growing AT‐1, AT‐2, and MAT‐Lu tumors), however, no expression of keratin specific for luminal cells was detected. In addition, several of the most advanced sublines (i.e., AT‐1, AT‐2, and MAT‐Lu) were negative using any of the keratin antibodies. In contrast, several of the other sublines with the most advanced degree of progression (i.e., the anaplastic, very fast growing MAT‐LyLu tumor derived from the AT‐1 subline; and the anaplastic, very fast growing AT‐3 tumor, derived from the HI‐F subline), however, were positively stained with the keratin antibody specific for the luminal cells.

By use of the keratin antibody specific for the basal cells of the normal rat prostate, the basal tumor cells of the well‐differentiated slow‐growing H and HI‐S tumor were positively stained. This positive staining for basal cell keratin was also found in the HI‐M and HI‐F tumors, while the AT‐1, AT‐2, MAT‐Lu, MAT‐LyLu, and AT‐3 were negative with this antibody. Thus, a loss in staining for basal cell keratin was consistently associated with the most advanced state of tumor progression.

Vimentin‐positive staining was demonstrated either alone or with keratin‐positive staining in part of the epithelial cancer cells of all the sublines. An increase in the positive staining for vimentin was consistently associated with a more advanced state of tumor progression. Desmin‐positive staining was found only in smooth cells present within the various tumor sublines.

These studies have demonstrated that different sublines of the Dunning prostatic cancer system can be distinguished on the basis of their pattern of intermediate filament protein expression and that these patterns are subject to dynamic regulation (both positive and negative) during the progression of prostatic cancer. Unfortunately, the pattern of IFP expression cannot be used alone to predict the metastatic ability of prostatic cancer.