Correlation between Laminin-5 γ&lt;sub&gt;2&lt;/sub&gt; Chain and Epidermal Growth Factor Receptor Expression in Esophageal Squamous Cell Carcinomas

Fukai, Yasuyuki; Masuda, Norihiro; Kato, Hiroyuki; Fukuchi, Minoru; Miyazaki, Tatsuya; Nakajima, Masahiro; Sohda, Makoto; Kuwano, Hiroyuki; Nakajima, Takashi

doi:10.1159/000087477

Cited by 31 publications

(28 citation statements)

References 78 publications

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“…This result was consistent with previous reports about ESCC (Yamamoto et al, 2001;Fukai et al, 2005) and suggested that laminin-332 at the invasive front of ESCC might have an important role in the process of tumour invasion. Laminin-332 has been reported to have potent cell migrationpromoting activity.…”

Section: Discussionsupporting

confidence: 93%

“…Sections with immunohistochemical staining in 430% of carcinoma cells at the invasive front were judged to be positive for laminin-332 as with the previous reports (Yamamoto et al, 2001;Fukai et al, 2005). The staining assessment was independently carried out by two of the authors (KI and YB) without any knowledge of either the clinical or survival data.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Laminin-332 interacts with two major epithelial integrin a3b1 and a6b4, and promotes the formation of two separate types of attachment structure, focal adhesion and stable anchoring contacts (Carter et al, 1990). In several types of carcinomas, laminin-332 has been reported to be highly expressed and to correlate well with poor patient prognosis (Pyke et al, 1995;Soini et al, 1996;Koshikawa et al, 1999;Matta et al, 1999;Ono et al, 1999;Yamamoto et al, 2001;Fukai et al, 2005). Laminin-332 is known to support cellular survival, proliferation and migration by activating many signal mediators through the ligation with a3b1 and a6b4 integrin, and to have important roles in tumour invasion and metastasis (Nguyen et al, 2000;Kariya and Miyazaki, 2004;Nikolopoulos et al, 2005).…”

mentioning

confidence: 99%

“…As to ESCC, there are two papers demonstrating that the immunohistochemically increased cytoplasmic expression of laminin-332 is correlated with poor prognosis (Yamamoto et al, 2001;Fukai et al, 2005). However, to our knowledge, there are no data showing the relationship between laminin-332 and cancer cell invasiveness, using oesophageal squamous cancer cell lines (ESCCs).…”

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confidence: 99%

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Laminin-332 promotes the invasion of oesophageal squamous cell carcinoma via PI3K activation

et al. 2008

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Laminin-332 is major component of epithelial basement membrane, and has an important role in cell migration and tumour invasion. Recently, the phosphatidylinositol 3-kinase (PI3K) activation induced by laminin-332 during carcinogenesis or tumour invasion has been highlighted in skin squamous cell carcinoma. The expression of laminin-332 in 126 resected oesophageal squamous cell carcinoma (ESCC) specimens was immunohistochemically examined to determine its associations with the clinicopathological characteristics, and the effect of laminin-332 on the invasiveness and the PI3K activation was assessed by in vitro experiments using ESCC cell lines (ESCCs). Sections with immunostaining signals in 430% cancer cells, which were observed in 55 of 126 cases, were judged to be positive for laminin-332. The positivity was significantly correlated with pTNM stage and poor prognosis. Inactivation of the PI3K pathway by laminin-332 blocking antibody suppressed the invasiveness of TE8 cell line, which secreted laminin-332 at high level and had high PI3K activity. The addition of the purified laminin-332 activated the PI3K pathway and increased the invasiveness of TE11 cell line, which secreted laminin-332 at lower level and had low PI3K activity. The deactivation of PI3K pathway using the PI3K inhibitor decreased the invasiveness of ESCCs and the secretion of laminin-332 in vitro. The expression of laminin-332 was one of the prognostic factors of ESCC. Laminin-332 could provide the autocrine positive-feedback loop through PI3K activation, contributing the invasive ability. Therefore, the inhibitor of PI3K pathway might be useful as the anticancer therapies for ESCC.

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Section: Discussionsupporting

confidence: 93%

Section: Immunohistochemistrymentioning

confidence: 99%

mentioning

confidence: 99%

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Laminin-332 promotes the invasion of oesophageal squamous cell carcinoma via PI3K activation

et al. 2008

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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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Altered expression of the urokinase receptor homologue, C4.4A, in invasive areas of human esophageal squamous cell carcinoma

Hansen

Lærum

Illemann

et al. 2007

Intl Journal of Cancer

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C4.4A is a glycolipid-anchored membrane protein with structural homology to the urokinase-type plasminogen activator receptor (uPAR). Although C4.4A was identified as a metastasis-associated protein little is known about its actual expression and possible function in malignant disease. In the present study, we have therefore analyzed the expression of C4.4A in 14 esophageal squamous cell carcinomas (ESCC). Normal squamous esophageal epithelium shows a strong cell surface associated C4.4A expression in the suprabasal layers, whereas basal cells are negative. Upon transition to dysplasia and carcinoma in situ the expression of C4.4A is abruptly and coordinately weakened. Double immunofluorescence staining of normal and dysplastic tissue showed that C4.4A colocalizes with the epithelial cell surface marker E-cadherin in the suprabasal cells and has a complementary expression pattern compared to the proliferation marker Ki-67. A prominent, but frequently intracellular, C4.4A expression reappeared in tumor cells located at the invasive front and local lymph node metastases. Because C4.4A was reported previously to be a putative laminin-5 (LN5) ligand, and both proteins are expressed by invasive tumor cells, we analyzed the possible coexpression of C4.4A and the c2-chain of LN5 (LN5-c2). Although these proteins are indeed expressed by either neighboring cancer cells or in a few cases even coexpressed by the same cells in the tumor front and metastases, we found no evidence for a general colocalization in the extracellular compartment by confocal microscopy. In conclusion, C4.4A is expressed during invasion and metastasis of human ESCC and may thus provide a new histological marker in this disease. ' 2007 Wiley-Liss, Inc.Key words: laminin-5; invasion; metastasis; microenvironment; uPAR Patients diagnosed with esophageal squamous cell carcinoma (ESSC) have a very poor prognosis.1 The explanation for the severe clinical behavior of this cancer is found in its extremely aggressive invasive character, despondently reflected by the 10% 5-year survival rate.2 In the majority of ESCC patients the cancer has already invaded the underlying muscle at the time of diagnosis, and in more than 50% of the cases the cancer cells have formed distant metastases.3,4 Because invasion and metastasis are considered major prognostic determinants in ESCC, there is a great interest in elucidating the mechanisms behind these processes.1 Activation of extracellular proteases and alterations in the binding abilities and expression of cell adhesion molecules (CAMs) are well-consolidated events in cancer cell dissemination, but more information at the molecular level is needed in order to develop intervention strategies and refine prognostic evaluations. 5-7A significant focus on identifying and investigating various new molecules as potential prognostic and diagnostic markers of cancer invasion and metastasis has developed during the last decade. C4.4A is an example of such a molecule. 8,9 This protein is a close relative of the urokinase-type p...

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Correlation between Laminin-5 γ<sub>2</sub> Chain and Epidermal Growth Factor Receptor Expression in Esophageal Squamous Cell Carcinomas

Cited by 31 publications

References 78 publications

Laminin-332 promotes the invasion of oesophageal squamous cell carcinoma via PI3K activation

Laminin-332 promotes the invasion of oesophageal squamous cell carcinoma via PI3K activation

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

Altered expression of the urokinase receptor homologue, C4.4A, in invasive areas of human esophageal squamous cell carcinoma

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