Investigation into the Mechanism of the Loss of Laminin 5 (α3β3γ2) Expression in Prostate Cancer

Abstract

Laminin 5 is a pivotal hemidesmosomal protein involved in cell stability, migration, and anchoring filament formation. Protein and gene expression of the alpha3, beta3, and gamma2 chains of laminin 5 were investigated in normal and invasive prostate carcinoma using immunohistochemistry, Northern analysis, and in situ hybridization. Laser capture microdissection of normal and carcinomatous glands, in conjunction with RNA amplification and reverse Northern analysis, were used to confirm the gene expression data. Protein and mRNA expression of all three laminin 5 chains were detected in the basal cells of normal glands. In contrast, invasive prostate carcinoma showed a loss of beta3 and gamma2 protein expression with variable expression of alpha3 chains. Despite the loss of protein expression, there was retention of beta3 and gamma2 mRNA expression as detected by in situ hybridization, Northern and reverse Northern analysis. Our findings imply that an altered mechanism of translation of beta3 or gamma2 mRNAs into functional proteins contributes to failure of anchoring filaments and hemidesmosomal formation. The resultant hemidesmosome instability or loss would suggest a less stable epithelial-stromal junction, increased invasion and migration of malignant cells, and disruption of normal integrin signaling pathways.

Myofibroblastic stromal reaction and expression of tenascin-C and laminin in prostate adenocarcinoma

“…37 Few other previous investigations showed decreased and disordered laminin expression in prostate carcinoma compared to benign glands. 25,29,30,[37][38][39][40] Laminin was also poorly expressed around glands with PIN, and especially accentuated loss of laminin was noted in cases with increased tenascin expression. 25 Current study confirmed results of previous investigations of laminin expression in prostate carcinoma.…”

“…25 Current study confirmed results of previous investigations of laminin expression in prostate carcinoma. 25,29,30,[37][38][39][40] Laminin was decreased in carcinoma compared to adjacent peritumourous tissue and BPH while peritumourous tissue and BPH showed similar pattern of laminin expression. We found no differences in laminin expression between Gleason pattern 3 and 4 carcinomas.…”

Laminin‐γ2 overexpression in head‐and‐neck squamous cell carcinoma

“…Although expression of laminin-5 may be lost during malignant progression of some tissues, such as prostatic epithelium, 22 microarray analysis has revealed that plating prostate cancer cells on a laminin-5 matrix can regulate expression of proteins involved in signal transduction, adhesion, proliferation and cell structure. 23 Therefore, overexpression of laminin-5 is likely to deregulate a number of biologic processes and to play a key role in the development of many tumors.…”

Immunohistochemical and molecular expression of laminin-332 gamma-2 chain in canine mammary tumors

“…The integrin molecules are mainly involved in cell adherence to extracellular matrix, and they are components of the hemidesmosome that bind to a specific site (RGD) in the laminin-332, establishing the link between the basal area of epithelial cells and the basal lamina (Hao et al, 2001). In normal tissues, laminin-332 acts to tether cells and inhibits their movement by inducing assembly of stable adhesive devices called hemidesmosomes.…”