Loss of laminin‐5 in the epithelium–stroma interface: an immunohistochemical marker of malignancy in epithelial lesions of the breast

Henning, Kathrin; Berndt, Alexander; Katenkamp, D.; Kosmehl, Hartwig

doi:10.1046/j.1365-2559.1999.00634.x

Cited by 52 publications

(42 citation statements)

References 24 publications

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“…Supporting our findings, loss of laminin 5 expression is also observed in invasive breast carcinomas and dedifferentiated mammary carcinoma cells (Henning et al, 1999;Miller et al, 2001). Our results suggest that altered expression and activation of laminin receptors like a6b4 during migration and local invasion of epithelial tumor cells (Rabinovitz and Mercurio, 1997;O'Connor et al, 1998) might not apply for dedifferentiated 'mesenchymal' cells after EMT.…”

Section: Introductionsupporting

confidence: 86%

“…In line with this, laminin 5 expression was lost in invasive, dedifferentiated breast carcinomas (Henning et al, 1999) and dedifferentiated, E-cadherin-negative breast carcinoma cells (MDA-MB-231; Miller et al, 2001). We thus assume that EMT abolishes formation or function of this integrin, which in polarized epithelial cells is restricted to cell-cell and cell-basement membrane contact areas and can be mobilized and activated during migration and local invasion of epithelial carcinoma cells after loss of polarity (O'Connor et al, 1998;Rabinovitz and Mercurio, 1997).…”

Section: Discussionsupporting

confidence: 60%

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Tumor cell invasiveness correlates with changes in integrin expression and localization

et al. 2005

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In nontumorigenic mammary epithelial cells (EpH4), transforming growth factor-b (TGFb1) causes cell cycle arrest/apoptosis, but induces epitheliomesenchymal transition (EMT) in Ha-Ras-transformed EpH4 cells (EpRas). EMT is closely correlated with late-stage tumor progression and results in fibroblastic, migratory cells displaying a mesenchymal gene expression program (FibRas). EpRas and FibRas cells showed strongly increased cell substrate adhesion to fibronectin, collagens I/IV and laminin 1. Furthermore, Ras transformation caused enhanced or de-novo expression of the integrin subunits b1, a2 and a3, or a5 and a6, respectively, the latter subunits being even more strongly expressed in FibRas cells. Importantly, polarized EpRas cells expressed integrin subunits b1 and a6 at distinct (apical and lateral) membrane domains, while FibRas cells coexpressed these integrins and a5 at the entire plasma membrane. During EMT, EpRas cells formed an a5b1 complex and deposited its ligand fibronectin into the extracellular matrix. Function-blocking a5 antibodies attenuated migration, and caused massive apoptosis in EpRas cells undergoing TGFb1-induced EMT in collagen gels, but failed to affect EpRas-or FibRas-derived structures. We conclude that functional a5b1 integrin is centrally implicated in EMT induction. Importantly, FibRas cells also failed to deposit the a6b4 ligand laminin 5, suggesting that a6b4 is no longer functional after EMT and replaced by mesenchymal integrins such as a5b1.

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Section: Introductionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 60%

Tumor cell invasiveness correlates with changes in integrin expression and localization

et al. 2005

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“…According to Henning et al (1999), the IHC demonstration of laminin-332 may serve as a marker of benignity in epithelial breast lesions. Fujita et al (2005) observed that chains of laminin-332 were expressed in the ductal epithelium basement membranes of the breast and diminished with tumor progression.…”

Section: Statisticalmentioning

confidence: 99%

“…They are believed to promote invasion of colon, breast, and skin cancer cells (Tsuruta et al, 2008). Along with clinical and pathological information, it has been used to assess tumor invasiveness (Hao et al, 1996;Henning et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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

Zuccari

Castro

Jardim

et al. 2011

Arq. Bras. Med. Vet. Zootec.

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Forty-eight cases of canine mammary cancer were investigated to evaluate the immunohistochemical distribution of the γ2 chain of laminin-332. Tumor cells were compared to a pool of normal mammary tissues using quantitative RT-PCR. The western blot was performed in eight tumor samples as complementary test to evaluate protein integrity. Immunohistochemistry experiments showed negative, focal, and weak expression of laminin-332 γ2 in tumors with the worst prognosis. Quantitative PCR revealed downregulation of the gene in 27 (56.2%) of the animals. Out of the 16 dogs with γ2 chain overexpression, seven were still alive. The western blot results showed bands generation of 36, 50, and 98kDa, suggesting degradation of laminin-332 γ2 in malignant tumors. The results suggest that, in the future, low expression and/or degradation of laminin-332 γ2 chain in canine mammary tumors may be used as an indicator of malignant potential. However, further studies are necessary to corroborate these results. Palavras-chave: cão, molécula de adesão, câncer, western blot, RT-PCR

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“…Laminin-5, which consists of a3, b3, and c2 chains, is localized in epithelial basement membranes, functions as a ligand for integrins, and plays an important role in cell migration and adhesion [15,16]. Some studies have reported that laminin c2 is expressed at the invasive front in tumor cells, while others demonstrated that loss of laminin c2 in the epithelium-stroma interface is an immunohistochemical marker of malignancy in epithelial lesions [17][18][19][20][21]. Laminin c2 expression patterns are divided into two distinct types, cytoplasmic staining and extracellular staining.…”

Section: Introductionmentioning

confidence: 99%

Clinicopathological significance of MMP-7, laminin γ2 and EGFR expression at the invasive front of gastric carcinoma

et al. 2013

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Background For several types of cancer, including gastric cancer (GC), tumor cells at the invasive front are considered to have a more aggressive behavior compared with those in the more central region. The aim of the present study was to analyze the expression of MMP-7, laminin c2 and EGFR in a large number of GCs and to investigate how these expression patterns correlate with clinicopathologic parameters, infiltrative patterns, histology or mucin phenotype. Methods We immunohistochemically examined the expression of MMP-7, laminin c2 and EGFR using a tissue microarray analysis of 790 GCs, and evaluated their clinicopathological significance. Results MMP-7, cytoplasmic laminin c2, extracellular laminin c2 and EGFR expression were observed in 25, 25, 8 and 21 % of the 790 GC cases, respectively. Expression of MMP-7, cytoplasmic laminin c2 and EGFR was associated with advanced T grade, N grade and tumor stage. Extracellular laminin c2 expression was not associated with any clinicopathologic parameters, infiltrative patterns, histology or mucin phenotype. Furthermore, we investigated the correlations of MMP-7, laminin c2 and EGFR expression. MMP-7 expression was significantly more frequent in positive expression of cytoplasmic laminin c2 than negative cases, and EGFR expression was significantly more frequent in positive expression of cytoplasmic laminin c2 and MMP-7.

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Loss of laminin‐5 in the epithelium–stroma interface: an immunohistochemical marker of malignancy in epithelial lesions of the breast

Cited by 52 publications

References 24 publications

Tumor cell invasiveness correlates with changes in integrin expression and localization

Tumor cell invasiveness correlates with changes in integrin expression and localization

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

Clinicopathological significance of MMP-7, laminin γ2 and EGFR expression at the invasive front of gastric carcinoma

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