In situ hybridization analysis of genes coding collagen IV alpha1 chain, laminin beta1 chain, and S-laminin in prostate tissue and prostate cancer: increased basement membrane gene expression in high-grade and metastatic lesions.
BACKGROUND
Recent immunohistochemical data have shown that invasive prostate cancer cells are separated from the host tissue by basement membranes (BM), and express associated adhesive molecules that bind to these de novo synthesized extracellular matrices.


METHODS
In the present study, we used in situ hybridization techniques to determine steady-state levels of genes coding BM components (alpha1 chain of collagen IV, laminin beta1 chain, and S-laminin) in prostate tissue obtained from 15 radical prostatectomy specimens and 5 lymph node metastases of common prostatic adenocarcinomas.


RESULTS
In benign prostate tissue, transcripts of these genes were detected predominantly in the basal cell layer, indicating that components of epithelial BMs are synthesized by basal cells and not by stromal cells. The cancerous lesions investigated revealed increasing collagen IV, laminin beta1 chain, and S-laminin mRNA levels when compared with benign prostate tissue. The highest steady-state levels were found in high grade (primary Gleason grade 4 and 5) carcinoma and lymph node metastases, and were predominantly localized in epithelial compartments of the cancerous tissue.


CONCLUSIONS
These findings indicate that neoplastic BM in prostatic adenocarcinoma derive from tumor cells and not from the host tissue. Increasing transcriptional activities of genes coding BM components detected in poorly differentiated and metastatic lesions may accelerate the BM-forming process, which probably contributes to the ability of tumor cells to penetrate the extracellular matrix during the process of stromal invasion and metastasis.
Department of Pathology, University of the Saarland, Homburg/Saar, Germany.
C
C
Pföhler
T
T
Fixemer
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V
Jung
S
S
Dooley
K
K
Remberger
H
H
Bonkhoff
D000230:Adenocarcinoma / Q000235:genetics* / Q000556:secondary; D000368:Aged; D001485:Basement Membrane / Q000502:physiology; D003094:Collagen / Q000235:genetics*; D024141:Collagen Type IV; D004847:Epithelial Cells; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D007797:Laminin / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010446:Peptide Fragments / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D014158:Transcription, Genetic
D024141:Collagen Type IV; D007797:Laminin; D010446:Peptide Fragments; C065384:collagen type IV alpha1 (531-543); C058783:laminin beta2; D003094:Collagen