L1 Cell adhesion molecule (L1CAM) expression at the cancer invasive front is a novel prognostic marker of pancreatic ductal adenocarcinoma

Tsutsumi, Shinji; Morohashi, Satoko; Kudo, Yasuyuki; Akasaka, Harue; Ogasawara, Hiroshi; Ono, Masashi; Takasugi, Kaori; Ishido, Keinosuke; Hakamada, Kenichi; Kijima, Hiroshi

doi:10.1002/jso.21880

Cited by 40 publications

(33 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We defined the invasive front as the front edge between the tumor and the stromal tissues. When the proportion of cancer cells positive for RacGAP1 at the invasive front was C10 %, the cancer was defined as being RacGAP1-positive, and the remainder of the tumor was defined as Rac-GAP1-negative at a magnification of 2009 in reference to previous report [18]. Each sample was scored in a blinded manner by two investigators (T. S. and Y.…”

Section: Immunohistochemical Evaluationmentioning

confidence: 99%

Clinical significance of RacGAP1 expression at the invasive front of gastric cancer

et al. 2014

View full text Add to dashboard Cite

Background Rac GTPase activating protein 1 (RacGAP1) plays a regulatory role in cell growth, transformation and metastasis. The aim of this study was to clarify the association between RacGAP1 expression and clinical outcome in patients with gastric cancer. Methods A total of 232 gastric cancer patients in our institute who underwent surgery without preoperative treatments were enrolled in this study. We investigated RacGAP1 expression using immunohistochemistry (IHC) and evaluated IHC scores calculated by the percentage of positive cells and intensity and its expression at the invasive front. RACGAP1 expression was also assessed. Results RacGAP1 expression was observed in the nuclei of gastric cancer cells. Evaluation by IHC score showed no significant correlations with clinicopathological variables except for histological differentiation. In transcriptional analyses, RACGAP1 expression was elevated in diffuse type gastric cancer than intestinal type without a significant difference. We observed significant correlations of Rac-GAP1 protein expression at the invasive front with older age, tumor size, lymph node metastasis, lymphatic invasion, vascular invasion and advanced stage. Patients with RacGAP1 protein expression at the invasive front had significantly poorer prognosis than those without it (P \ 0.0001). In multivariate analysis, lymph node metastasis, distant metastasis and positive RacGAP1 expression at the invasive front were independent prognostic factors (lymph node metastasis: P = 0.0106; distant metastasis: P = 0.0012; RacGAP1: P = 0.0011). Conclusions RacGAP1 expression at the invasive front in gastric cancer was significantly correlated with factors reflecting tumor progression and poor prognosis. Our data suggest that RacGAP1 might play important roles in the progression of gastric cancer.

show abstract

Section: Immunohistochemical Evaluationmentioning

confidence: 99%

Clinical significance of RacGAP1 expression at the invasive front of gastric cancer

et al. 2014

View full text Add to dashboard Cite

show abstract

“…For several types of cancer, tumor cells at the invasive front are considered to have more aggressive behavior compared with those in the more central region [41][42][43] and are characterized by a dynamic process referred to as epithelial mesenchymal transition (EMT) [44,45]. EMT is considered to be a transient and reversible process, and represents only one of the several steps required for tumor progression via invasion and metastatic spread [46], because it has also been implicated in the fundamental steps of tumorigenesis, such as invasion and metastasis [47].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2013

View full text Add to dashboard Cite

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.

show abstract

“…A recent study revealed that elevated L1CAM levels were associated with shorter survival in patients with pancreatic ductal adenocarcinoma (12). In addition, studies on resected tumor samples from colorectal (32), ovarian (9), and melanoma (33) cancer patients have linked L1CAM overexpression to poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…Deregulated expression of members of all major cell adhesion molecule families [integrins, selectins, cadherins, and the immunoglobulin (Ig) superfamily] is frequently reported in human cancers (8). One such molecule, L1 cell adhesion molecule (L1CAM), is aberrantly expressed in several cancer types, including ovarian (9), melanoma (10), breast (11), pancreatic (12), and colon cancers (13). L1CAM is a type I membrane glycoprotein of the Ig-like superfamily, consisting of 6 Ig-like domains and 5 fibronectin-type III repeats, followed by a single-pass transmembrane region and a highly conserved cytoplasmic tail (14).…”

Section: Introductionmentioning

confidence: 99%

L1 Cell Adhesion Molecule Promotes Tumorigenicity and Metastatic Potential in Non–Small Cell Lung Cancer

Hai

Zhu

Bandarchi

et al. 2012

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Non-small cell lung cancer (NSCLC) is a highly metastatic cancer with limited treatment options, thus requiring development of novel targeted therapies. Our group previously identified L1 cell adhesion molecule (L1CAM) expression as a member of a prognostic multigene expression signature for NSCLC patients. However, there is little information on the biologic function of L1CAM in lung cancer cells. This study investigates the functional and prognostic role of L1CAM in NSCLC.Experimental Design: Cox proportional hazards regression analysis was done on four independent published mRNA expression datasets of primary NSCLCs. L1CAM expression was suppressed by shorthairpin RNA (shRNA)-mediated silencing in human NSCLC cell lines. Effects were assessed by examining in vitro migration and invasion, in vivo tumorigenicity in mice, and metastatic potential using an orthotopic xenograft rat model of lung cancer.Results: L1CAM is an independent prognostic marker in resected NSCLC patients, with overexpression strongly associated with worse prognosis. L1CAM downregulation significantly decreased cell motility and invasiveness in lung cancer cells and reduced tumor formation and growth in mice. Cells with L1CAM downregulation were deficient in constitutive extracellular signal-regulated kinase (Erk) activation. Orthotopic studies showed that L1CAM suppression in highly metastatic lung cancer cells significantly decreases spread to distant organs, including bone and kidney.Conclusion: L1CAM is a novel prometastatic gene in NSCLC, and its downregulation may effectively suppress NSCLC tumor growth and metastasis. Targeted inhibition of L1CAM may be a novel therapy for NSCLC.

show abstract

L1 Cell adhesion molecule (L1CAM) expression at the cancer invasive front is a novel prognostic marker of pancreatic ductal adenocarcinoma

Abstract: L1CAM could play an important role in the invasive process in vivo, and is thought to be a good indicator of prognosis in PDAC.

Cited by 40 publications

References 29 publications

Clinical significance of RacGAP1 expression at the invasive front of gastric cancer

Clinical significance of RacGAP1 expression at the invasive front of gastric cancer

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

L1 Cell Adhesion Molecule Promotes Tumorigenicity and Metastatic Potential in Non–Small Cell Lung Cancer

Contact Info

Product

Resources

About