Laminin-5^|^gamma;2 chain expression is associated with tumor cell invasiveness and prognosis of lung squamous cell carcinoma

Masuda, Ryosuke; Kijima, Hiroshi; Imamura, Naoko; Aruga, Naohiro; Nakazato, Kenei; Oiwa, Kana; Nakano, Takayuki; Watanabe, Hajime; Ikoma, Yoichiro; Tanaka, Makiko; Inokuchi, Sadaki; Iwazaki, Masayuki

doi:10.2220/biomedres.33.309

Cited by 27 publications

(25 citation statements)

References 32 publications

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“…High LAMC2 was associated with a higher risk of recurrence (P = 0.027) and death (P = 0.012) in ADC but not in SCC (Figure 6f), although others, by stratifying LAMC2 expression based on the stromal types or LAMC2 distribution in tumors, showed that high LAMC2 expression in lung SCC with fibrous stroma composition or in invasive front of SCC was correlated with tumor aggressiveness. 39,40 In line with the latter, overexpression of LAMC2 in H1703, a lung SCC cell line, augmented migration and invasion as compared with mock controls (Supplemental Figure 6a). Whether LAMC2 may have a similar role in lung SCC as in lung ADC remains to be investigated.…”

Section: Resultsmentioning

confidence: 53%

LAMC2 enhances the metastatic potential of lung adenocarcinoma

et al. 2015

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Lung cancer is the number one cancer killer, and metastasis is the main cause of high mortality in lung cancer patients. However, mechanisms underlying the development of lung cancer metastasis remain unknown. Using genome-wide transcriptional analysis in an experimental metastasis model, we identified laminin γ2 (LAMC2), an epithelial basement membrane protein, to be significantly upregulated in lung adenocarcinoma metastatic cells. Elevated LAMC2 increased traction force, migration, and invasion of lung adenocarcinoma cells accompanied by the induction of epithelial-mesenchymal transition (EMT). LAMC2 knockdown decreased traction force, migration, and invasion accompanied by EMT reduction in vitro, and attenuated metastasis in mice. LAMC2 promoted migration and invasion via EMT that was integrin β1-and ZEB1-dependent. High LAMC2 was significantly correlated with the mesenchymal marker vimentin expression in lung adenocarcinomas, and with higher risk of recurrence or death in patients with lung adenocarcinoma. We suggest that LAMC2 promotes metastasis in lung adenocarcinoma via EMT and may be a potential therapeutic target. Cell Death and Differentiation (2015) 22, 1341-1352; doi:10.1038/cdd.2014.228; published online 16 January 2015Lung cancer is the leading cause of cancer-related death. 1 Non-small-cell lung cancer (NSCLC) accounts for~80-85% of lung cancers. 2 Only 20-30% of NSCLC are radically resectable and the majority of lung cancer patients succumb to the disease. The high mortality of NSCLC is largely attributable to late diagnosis, when metastases are present. 2 The molecular mechanisms governing metastasis of NSCLC remain poorly understood.Metastasis is a complex, multistep process, involving migration and invasion of malignant cells from the primary tumor to blood vessels, intravasation, and survival in the circulation, and ultimately extravasation, colonization, and formation of secondary tumor at distant target organs. 3 Each of these events is classically driven by the acquisition of genetic and/or epigenetic traits in tumor cells and the cooperation of nonneoplastic stromal cells. Increased or decreased expression of several genes in tumors has been found to be correlated with metastasis. 3 However, specific gene alterations that drive NSCLC metastasis remain largely elusive.Laminin γ2 (LAMC2) is a subunit of the heterotrimeric glycoprotein laminin-332 (LAM-332, formerly laminin-5), consisting of the α3, β3, and γ2 chains. Although LAMC2 is an important structural component of the epithelial basement membrane (BM) in various normal tissues, 4 there is an emerging evidence for a pathological role of LAMC2 monomer in cancer. It has been demonstrated that LAMC2 protein expression correlates with clinical outcome of stage I lung adenocarcinoma (ADC) patients. 5,6 In addition, noncontinuous expression pattern of LAMC2 predicts the prognosis of esophageal squamous cell carcinoma (SCC), 7 and secreted LAMC2 in the serum is associated with the aggressiveness of pancreatic cancer. 8 Besides, LAMC2 monom...

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Section: Resultsmentioning

confidence: 53%

LAMC2 enhances the metastatic potential of lung adenocarcinoma

et al. 2015

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“…This association is highly expected, concerning that tumor budding is a morphologic marker of tumor invasion and laminin‐5 γ2 is capable to generate a migratory tumor cell phenotype, giving tumor cells the necessary mobility to invade . Several studies have identified the occurrence of tumor budding as an important marker for poor prognosis in epithelial malignancies , including OSCC . Even though higher laminin‐5 γ2 expression has been associated with high‐intensity tumor budding in cancer , to the best of our knowledge, this is the first report showing this association in OSCC.…”

Section: Discussionmentioning

confidence: 74%

“…Several studies have identified the occurrence of tumor budding as an important marker for poor prognosis in epithelial malignancies , including OSCC . Even though higher laminin‐5 γ2 expression has been associated with high‐intensity tumor budding in cancer , to the best of our knowledge, this is the first report showing this association in OSCC. Regardless of the association between higher laminin‐5 γ2 expression and high‐intensity tumor budding, it is important to remark that higher expression of laminin‐5 γ2 was also reported in incipient OSCC, suggesting that it should be important in the early steps of tumor invasion .…”

Section: Discussionmentioning

confidence: 78%

Laminin‐5 gamma 2 chain expression is associated with intensity of tumor budding and density of stromal myofibroblasts in oral squamous cell carcinoma

Júnior

Rocha

Leite

et al. 2013

J Oral Pathology Medicine

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“…Lung cancer is evaluated according to morphological features, including histological type, histological differentiation, pleural invasion, blood vessel invasion and lymphatic invasion (8–10). Evaluations of cancer in other organs include histological factors, such as the INF pattern and stromal type (4–7,29,30). Therefore, the present study considered it important to evaluate these factors in lung cancer, in combination with the conventional factors.…”

Section: Discussionmentioning

confidence: 99%

Lymphatic invasion is a significant indicator of poor patient prognosis in lung squamous cell carcinoma

Masuda

Kijima

Nito

et al. 2017

Molecular Medicine Reports

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Pathological stage is the most important prognostic factor in patients with lung cancer, and is defined according to the tumor node metastasis classification system. The present study aimed to investigate the clinicopathological significance of lymphatic invasion in 103 patients who underwent surgical resection of lung squamous cell carcinoma (SqCC). The patients were divided into two groups, according to the degree of lymphatic invasion: Those with no or mild lymphatic invasion (ly0-1) and those with moderate or severe lymphatic invasion (ly2-3). Ly2-3 was associated with tumor size (P=0.028), lymph node metastasis (P<0.001), venous invasion (P=0.001) and histological differentiation (P=0.047). Statistical analysis using the Kaplan-Meier method and the log-rank test indicated that overall survival was significantly reduced in patients with ly2-3 compared with those with ly0-1 (P<0.001). Multivariate analysis identified ly2-3 as an independent predictor of mortality (hazard ratio, 2.580; 95% confidence interval, 1.376–4.839). In conclusion, moderate or severe lymphatic invasion (ly2-3) indicated a high malignant potential and may be considered an independent predictor of poor prognosis in patients with SqCC of the lung.

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Laminin-5^|^gamma;2 chain expression is associated with tumor cell invasiveness and prognosis of lung squamous cell carcinoma

Cited by 27 publications

References 32 publications

LAMC2 enhances the metastatic potential of lung adenocarcinoma

LAMC2 enhances the metastatic potential of lung adenocarcinoma

Laminin‐5 gamma 2 chain expression is associated with intensity of tumor budding and density of stromal myofibroblasts in oral squamous cell carcinoma

Lymphatic invasion is a significant indicator of poor patient prognosis in lung squamous cell carcinoma

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