CD98 Expression Is Associated with Poor Prognosis in Resected Non-Small-Cell Lung Cancer with Lymph Node Metastases

Kaira, Kyoichi; Oriuchi, Noboru; Imai, Hisao; Shimizu, Kimihiro; Yanagitani, Noriko; Sunaga, Noriaki; Hisada, Takeshi; Kawashima, Osamu; Kamide, Yosuke; Ishizuka, Tamotsu; Kanai, Yoshikatsu; Nakajima, Takashi; Mori, Masatomo

doi:10.1245/s10434-009-0685-0

Cited by 66 publications

(65 citation statements)

References 33 publications

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“…SLC7A5 is overexpressed in many cancer types, including SCLC, and its expression levels are usually correlated to cancer progression and aggressiveness [14][15][16]. We demonstrated that in SCLC cells, similarly to other tumor types [17][18][19], suppression of SLC7A5 expression has an anti-proliferative effect.…”

Section: Discussionmentioning

confidence: 66%

miR-126 inhibits proliferation of small cell lung cancer cells by targeting SLC7A5

Margitai²,

et al. 2011

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Edited by Tamas Dalmay Keywords:Small cell lung cancer miR-126 SLC7A5 G1 delay a b s t r a c t Despite intensive efforts to improve therapies, small cell lung cancer (SCLC) still has a dismal median survival of 18 months. Since miR-126 is under-expressed in the majority of SCLC tumors, we investigated the effect of miR-126 overexpression on the proliferation and cell cycle distribution of H69 cells. Our results demonstrate that miR-126 inhibits proliferation of H69 cells, by delaying the cells in the G1 phase. Short interfering RNA (siRNA) mediated suppression of SLC7A5, a predicted target of mir-126, has the same effect on H69 cells. We also show for the first time that SLC7A5 is a direct target of miR-126.

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Section: Discussionmentioning

confidence: 66%

miR-126 inhibits proliferation of small cell lung cancer cells by targeting SLC7A5

Margitai²,

et al. 2011

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“…Recently, 4F2hc has been documented to be an independent prognostic factor for predicting poor outcome in thoracic neoplasms such as NSCLC and thymic epithelial tumors (10,23). In these studies, angiogenesis has an essential role on the development of 4F2hc expression, but it remains unknown how hypoxia and glucose metabolism are associated with the expression of 4F2hc.…”

Section: Discussionmentioning

confidence: 99%

“…Immunohistochemical staining was performed according to the procedure described in previous reports (10,15). The following antibodies were used: a rabbit polyclonal against Glut1 (AB15309, Abcam, Tokyo, Japan, 1:200 dilution); a rabbit polyclonal against Glut3 (AB15311, Abcam, 1:100 dilution); a rabbit monoclonal against hexokinase I (AB55144, Abcam, 1:200 dilution); a mouse monoclonal against HIF-1α (NB100-123, Novus Biologicals, Inc., Littleton, CO, 1:50 dilution); a monoclonal against VEGF (Immuno-Biological Laboratories Co., Ltd., Japan, 1:300 dilution); a mouse monoclonal against CD34 (Nichirei, Tokyo, Japan, 1:800 dilution); a mouse monoclonal against EGFR (Novovastra Laboratories Ltd., Newcastle, UK, 1:100 dilution); a rabbit polyclonal against phospho-Akt (Abcam, Tokyo, Japan, 1:200 dilution); a rabbit monoclonal against phospho-mTOR (Cell Signaling, 1:80 dilution); a rabbit monoclonal against phospho-S6K (Cell Signaling, 1:100 dilution) and a mouse monoclonal against p53 (D07; Dako, 1:50 dilution).…”

Section: Methodsmentioning

confidence: 99%

“…Recent studies have documented that 4F2hc expression is increased in a variety of carcinomas and has a crucial role on the tumor progression and metastasis of human neoplasms (8)(9)(10)(11)(12)(13)(14). Recent studies have described that the expression of 4F2hc correlates with cell proliferation and angiogenesis, and 4F2hc could be a significant prognostic factor for predicting poor outcome in non-small cell lung cancer (NSCLC) (10). However, little is known about how 4F2hc is associated with the pathogenesis and development of patients with pulmonary NE tumors.…”

Section: Introductionmentioning

confidence: 99%

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Expression of 4F2hc (CD98) in pulmonary neuroendocrine tumors

Kaira

Ohde²,

Endo³

et al. 2011

Oncol Rep

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Abstract. 4F2hc (CD98) has been associated with tumor growth, and is highly expressed in various tumors. The aim of this study was to evaluate the clinicopathological significance of 4F2hc expression in pulmonary neuroendocrine (NE) tumors. Surgically-resected patient tumors including 16 large cell neuroendocrine carcinoma (LCNEC), 12 small cell lung cancer (SCLC), 1 atypical carcinoid (AC) and 5 typical carcinoid (TC) samples were included in this study. Tumor sections were immunohistochemically stained for 4F2hc (CD98), glucose transporter 1 (Glut1) and 3 (Glut3), hypoxia-inducible factor-1α (HIF-1α), hexokinase I, vascular endothelial growth factor (VEGF), microvessel density (CD34), epidermal growth factor receptor (EGFR), Akt/mammalian target of rapamycin (mTOR) signaling pathway (p-Akt, p-mTOR and p-S6K) and for a cell cycle regulator (p53). 4F2hc was overexpressed in 0% of the pulmonary carcinoids (TCs and ACs), 62.5% of the LCNECs and 50.0% of the SCLCs. A positive 4F2hc expression was significantly associated with age, histology and Glut1 expression. Moreover, a significant correlation was found between 4F2hc expression, and Glut1, HIF-1α, p-Akt, p-mTOR and p-S6K. The expression of 4F2hc was also significantly associated with poor overall survival. The expression of 4F2hc expression tended to increase from low-grade to high-grade pulmonary NE tumors. Our results suggest that 4F2hc may play a significant role in tumor progression, hypoxic conditions and poor outcome in patients with pulmonary NE tumors. IntroductionNeuroendocrine (NE) tumors of the lung arise from Kulchitzky cells, which are normally present in the bronchial mucosa and share the common morphological features of neuroendocrine tumors, including organoid nesting, palisading, rosettes, or a trabecular growth pattern. These tumors are represented by a wide range of pathological entities (1-5). It is now widely recognized that NE tumors of the lung include a spectrum that ranges from low-grade typical carcinoid (TC) and intermediate-grade atypical carcinoid (AC) to high-grade large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinomas (SCLC) (1-4). However, there has been no established clinical marker, which correlates with the response to the treatment and the prognosis in patients with pulmonary NE tumors. 4F2hc (CD98) is a disulphide-linked 125-kDa heterodimeric membrane glycoprotein, which is found on the cell surface of most normal cells. It was first identified on the cell surface of T lymphocytes (5). However, 4F2hc has been shown to be involved in the cellular proliferation, transformation, fusion, and adhesion and also in the L-type amino acid transport (LAT) system, in addition to regulating integrin activation, and therefore, integrin signaling and anchorage-independent growth. 4F2hc is reconstituted and expressed at high levels on the surface of many types of tumor cells. The overexpression of 4F2hc has been shown to result in cellular transformation (6,7). Recent studies have documented that 4F2hc expression is in...

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“…In patients with surgical excision, the stage was determined by operative and pathological findings. In patients with biopsy only, the stage was determined by diagnostic imaging including computed tomography and 2-[1 8 F]-fluoro-2-deoxy-D-glucose positron emission tomography ( 18 F-FDG PET). All surgical specimens were reviewed and classified according to the WHO classification (2,3) by an experienced lung pathologist who was unaware of clinical or imaging findings.…”

Section: Methodsmentioning

confidence: 99%

CD98 expression is associated with the grade of malignancy in thymic epithelial tumors

Kaira¹

2010

Oncol Rep

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Abstract. CD98 has been associated with tumor growth and is highly expressed in human neoplasms. The aim of this study was to evaluate the clinicopathological significance of CD98 expression in thymic epithelial tumors. Forty-nine patients with thymic epithelial tumors were included in this study. Tumor sections were stained by immunohistochemistry for CD98; vascular endothelial growth factor (VEGF); microvessels (CD31 and CD34); cell cycle control marker (p53); and apoptosis marker (Bcl-2). CD98 expression for low-risk thymomas, high-risk thymomas, and thymic carcinomas were 1 (4%) of 27, 9 (82%) of 11, and 11 (100%) of 11, respectively. There was positive correlation between CD98 and VEGF (p<0.001), microvessel density (CD31 and CD34) (p<0.001) and p53 (p<0.001). However, Bcl-2 showed no positive correlation with CD98 expression. The expression of CD98 were also significantly associated with the grade of malignancy in thymic epithelial tumors. Multivariate analysis revealed that overexpression of CD98 was a significant independent factor predicting a poor outcome in thymic epithelial tumors. CD98 expression was associated with the grade of malignancy in thymic epithelial tumors. Moreover, CD98 expression was closely correlated with angiogenesis and cell cycle control, and was useful for predicting poor outcome.

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CD98 Expression Is Associated with Poor Prognosis in Resected Non-Small-Cell Lung Cancer with Lymph Node Metastases

Abstract: In our limited series, CD98 is a pathological factor that predicts prognosis in resectable adenocarcinoma patients with N2 disease.

Cited by 66 publications

References 33 publications

miR-126 inhibits proliferation of small cell lung cancer cells by targeting SLC7A5

miR-126 inhibits proliferation of small cell lung cancer cells by targeting SLC7A5

Expression of 4F2hc (CD98) in pulmonary neuroendocrine tumors

CD98 expression is associated with the grade of malignancy in thymic epithelial tumors

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