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Analytical molecular pathology of epithelial-stromal interactions in the normal and neoplastic prostate
1Department of Pathology, University of the Saarland, Homburg/Saar, Germany. patfix@med-rz.uni-sb.de
Objective:
To review recent data on epithelial-stromal interactions, recognized as playing an important role in prostatic growth in vitro.
Study Design:
The present review summarizes recent data on gene expression of basement membrane (BM) components and related integrin receptors reported in human prostate tissue and discusses potential implications of these adhesive elements in prostatic carcinogenesis and tumor progression.
Results:
Benign glandular structures and premalignant prostatic lesions (prostatic intraepithelial neoplasia, high grade (HGPIN)) are surrounded by BM and form stable hemidesmosomes. Early stromal invasion is associated with the loss of both hemidesmosome-associated adhesive elements (laminin 5, collagen type VII, alpha 6, beta 4 integrins) and basal cell differentiation. Invasive tumor cells produce BM-like matrices and express related integrin receptors. Increasing transcriptional activity of BM encoding genes has been found in poorly differentiated and metastatic lesions.
Conclusion:
The inability of transformed cells to express hemidesmosome structures and related adhesive elements appears to be a crucial event in neoplastic progression of HGPIN to early stromal invasion and may account for the definitive loss of basal cell differentiation during this process. Formation of de novo synthesized BM and adhesion via specific receptors may significantly contribute to the ability of prostate cancer cells to penetrate the extracellular matrix during stromal invasion and metastasis.