Polarization, migration, and homotypical interactions among prostatic smooth muscle cells in a laminin 111-rich extracellular matrix.

Prostate cancer is a life-threatening condition worldwide. As the tumor progresses, smooth muscle cells (SMCs) become atrophic/dedifferentiated, within a series of stromal changes named stromal reaction. Here, we tested whether a laminin 111-rich extracellular matrix (Lr-ECM) could affect SMCs phenotype and differentiation status. Using time-lapse microscopy, image analyses, quantitative real-time reverse transcription polymerase chain reaction, immunohistochemistry and immunoblotting, and transmission electron microscopy, we showed that SMCs acquires a migratory behavior with a decreased expression of differentiation markers and relocation of focal adhesion kinase. SMCs set homotypic cell junctions and were active in autophagy/phagocytosis. Analysis of the migratory behavior showed that SMCs polarized and migrated toward each other, recognizing long-distance signals such as matrix tensioning. However, half of the cell population were immotile, irrespective of the nearest neighbor distance, suggesting they do not engage in productive interactions, possibly as a result of back-to-back positioning. In conclusion, the Lr-ECM, mimics the effects of the proliferating and infiltrating tumor epithelium, causing SMCs phenotypical change similar to that observed in the stromal reaction, in addition to a hitherto undescribed, stereotyped pattern of cell motility resulting from cell polarization.

Expression of laminin-5 γ2 chain in cutaneous pseudocarcinomatous hyperplasia.

BACKGROUND: Since the use of laminin-5 as a marker of invasiveness has been proposed by several authors, our objective was to compare the expression of this protein in pseudocarcinomatous hyperplasia and squamous cell carcinoma (SCC). METHODS: Sixty-four paraffin-embedded skin biopsy samples with diagnosis of epidermal hyperplasia (non-pseudocarcinomatous), pseudocarcinomatous hyperplasia, actinic keratosis/carcinoma in situ, microinvasive and frankly invasive SCC were obtained for immunohistochemical study. RESULTS: Adjacent normal epithelium and epidermal hyperplasia (non-pseudocarcinomatous) showed no staining. In pseudocarcinomatous hyperplasia, laminin-5 was positive, at least focally, in 14 of 16 (87.5%) samples and was concentrated in peripheral cells of elongated rete pegs and in migrating cells in dermis. In samples of microinvasive carcinoma (n = 7), the expression was observed in all cases and was concentrated in the leading edge of the tumor. All cases (n = 21) of frankly invasive SCC showed cells expressing laminin-5, at least focally. Well-differentiated areas of the tumor presented a pattern of expression in peripheral cells of tumor nests while a diffuse pattern of expression was observed in less differentiated areas. CONCLUSION: We showed that cytoplasmic laminin-5 expression should not be used as a criterion of malignancy and is not useful in distinguishing pseudocarcinomatous hyperplasia from microinvasive and well-differentiated SCC.