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L1CAM protein expression is associated with poor prognosis in non-small cell lung cancer.

Tischler V, Pfeifer M, Hausladen S, Schirmer U, Bonde AK, Kristiansen G, Sos ML, Weder W, Moch H, Altevogt P, Soltermann A - Mol. Cancer (2011)

Bottom Line: L1CAM protein expression was found in 25% of squamous cell carcinomas and 24% of adenocarcinomas and correlated with blood vessel invasion and metastasis (p < 0.05).In L1CAM-positive SK-LU-1 and SK-LC-LL cells matrigel invasion was decreased after L1CAM siRNA knockdown.L1CAM is a novel prognostic marker for NSCLCs that is upregulated by EMT induction and appears to be instrumental for enhanced cell invasion.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland. verena.tischler@usz.ch

ABSTRACT

Background: The L1 cell adhesion molecule (L1CAM) is potentially involved in epithelial-mesenchymal transition (EMT). EMT marker expression is of prognostic significance in non-small cell lung cancer (NSCLC). The relevance of L1CAM for NSCLC is unclear. We investigated the protein expression of L1CAM in a cohort of NSCLC patients. L1CAM protein expression was correlated with clinico-pathological parameters including survival and markers of epithelial-mesenchymal transition.

Results: L1CAM protein expression was found in 25% of squamous cell carcinomas and 24% of adenocarcinomas and correlated with blood vessel invasion and metastasis (p < 0.05). L1CAM was an independent predictor of survival in a multivariate analysis including pT, pN, and pM category, and tumor differentiation grade. L1CAM expression positively correlated with vimentin, beta-catenin, and slug, but inversely with E-cadherin (all p-values < 0.05). E-cadherin expression was higher in the tumor center than in the tumor periphery, whereas L1CAM and vimentin were expressed at the tumor-stroma interface. In L1CAM-negative A549 cells the L1CAM expression was upregulated and matrigel invasion was increased after stimulation with TGF-beta1. In L1CAM-positive SK-LU-1 and SK-LC-LL cells matrigel invasion was decreased after L1CAM siRNA knockdown.

Conclusions: A subset of NSCLCs with vessel tropism and increased metastasis aberrantly expresses L1CAM. L1CAM is a novel prognostic marker for NSCLCs that is upregulated by EMT induction and appears to be instrumental for enhanced cell invasion.

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L1CAM in A549. A) Stimulation of A549 cells with TGF-beta1 induces a mesenchymal phenotype whereas HGF does not alter cell morphology. Note that TGF-beta1 treatment affected the proliferation of A549 cells. B/C) A549 cells stimulated with TGF-beta1 show an EMT phenotype and increased L1CAM expression on mRNA and protein level. One representative experiment of n = 3 is shown. GAP-DH loading control. D) Matrigel invasion of A549 cells is enhanced by TGF-beta1 stimulation. The error bars represent mean values ± SEM. One representative experiment of n = 3 is shown.
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Figure 4: L1CAM in A549. A) Stimulation of A549 cells with TGF-beta1 induces a mesenchymal phenotype whereas HGF does not alter cell morphology. Note that TGF-beta1 treatment affected the proliferation of A549 cells. B/C) A549 cells stimulated with TGF-beta1 show an EMT phenotype and increased L1CAM expression on mRNA and protein level. One representative experiment of n = 3 is shown. GAP-DH loading control. D) Matrigel invasion of A549 cells is enhanced by TGF-beta1 stimulation. The error bars represent mean values ± SEM. One representative experiment of n = 3 is shown.

Mentions: The correlation of L1CAM expression with invasion in the TMA analysis prompted us to study the pro-invasive function of L1CAM in-vitro. A549 cells were treated for 7 days with 5ng/mL HGF or 10ng/mL TGF-beta1 and an EMT like phenotype was induced (Figure 4A). By RT-PCR analysis we found L1CAM, snail, slug, vimentin and beta-catenin mRNA upregulated in A549 cells after TGF-beta1 stimulation for 7 days (Figure 4B). In contrast, E-cadherin mRNA was downregulated in A549 cells (Figure 4B). Similar results were observed for another lung adenocarcinoma cell line H1395 (data not shown). On the protein level, TGF-beta1 induced increased L1CAM, vimentin and beta-catenin expression in A549 cells whereas E-cadherin was downregulated (Figure 4C). In a matrigel invasion assay, TGF-beta1 treatment augmented invasion of A549 cells (Figure 4D).


L1CAM protein expression is associated with poor prognosis in non-small cell lung cancer.

Tischler V, Pfeifer M, Hausladen S, Schirmer U, Bonde AK, Kristiansen G, Sos ML, Weder W, Moch H, Altevogt P, Soltermann A - Mol. Cancer (2011)

L1CAM in A549. A) Stimulation of A549 cells with TGF-beta1 induces a mesenchymal phenotype whereas HGF does not alter cell morphology. Note that TGF-beta1 treatment affected the proliferation of A549 cells. B/C) A549 cells stimulated with TGF-beta1 show an EMT phenotype and increased L1CAM expression on mRNA and protein level. One representative experiment of n = 3 is shown. GAP-DH loading control. D) Matrigel invasion of A549 cells is enhanced by TGF-beta1 stimulation. The error bars represent mean values ± SEM. One representative experiment of n = 3 is shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198986&req=5

Figure 4: L1CAM in A549. A) Stimulation of A549 cells with TGF-beta1 induces a mesenchymal phenotype whereas HGF does not alter cell morphology. Note that TGF-beta1 treatment affected the proliferation of A549 cells. B/C) A549 cells stimulated with TGF-beta1 show an EMT phenotype and increased L1CAM expression on mRNA and protein level. One representative experiment of n = 3 is shown. GAP-DH loading control. D) Matrigel invasion of A549 cells is enhanced by TGF-beta1 stimulation. The error bars represent mean values ± SEM. One representative experiment of n = 3 is shown.
Mentions: The correlation of L1CAM expression with invasion in the TMA analysis prompted us to study the pro-invasive function of L1CAM in-vitro. A549 cells were treated for 7 days with 5ng/mL HGF or 10ng/mL TGF-beta1 and an EMT like phenotype was induced (Figure 4A). By RT-PCR analysis we found L1CAM, snail, slug, vimentin and beta-catenin mRNA upregulated in A549 cells after TGF-beta1 stimulation for 7 days (Figure 4B). In contrast, E-cadherin mRNA was downregulated in A549 cells (Figure 4B). Similar results were observed for another lung adenocarcinoma cell line H1395 (data not shown). On the protein level, TGF-beta1 induced increased L1CAM, vimentin and beta-catenin expression in A549 cells whereas E-cadherin was downregulated (Figure 4C). In a matrigel invasion assay, TGF-beta1 treatment augmented invasion of A549 cells (Figure 4D).

Bottom Line: L1CAM protein expression was found in 25% of squamous cell carcinomas and 24% of adenocarcinomas and correlated with blood vessel invasion and metastasis (p < 0.05).In L1CAM-positive SK-LU-1 and SK-LC-LL cells matrigel invasion was decreased after L1CAM siRNA knockdown.L1CAM is a novel prognostic marker for NSCLCs that is upregulated by EMT induction and appears to be instrumental for enhanced cell invasion.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland. verena.tischler@usz.ch

ABSTRACT

Background: The L1 cell adhesion molecule (L1CAM) is potentially involved in epithelial-mesenchymal transition (EMT). EMT marker expression is of prognostic significance in non-small cell lung cancer (NSCLC). The relevance of L1CAM for NSCLC is unclear. We investigated the protein expression of L1CAM in a cohort of NSCLC patients. L1CAM protein expression was correlated with clinico-pathological parameters including survival and markers of epithelial-mesenchymal transition.

Results: L1CAM protein expression was found in 25% of squamous cell carcinomas and 24% of adenocarcinomas and correlated with blood vessel invasion and metastasis (p < 0.05). L1CAM was an independent predictor of survival in a multivariate analysis including pT, pN, and pM category, and tumor differentiation grade. L1CAM expression positively correlated with vimentin, beta-catenin, and slug, but inversely with E-cadherin (all p-values < 0.05). E-cadherin expression was higher in the tumor center than in the tumor periphery, whereas L1CAM and vimentin were expressed at the tumor-stroma interface. In L1CAM-negative A549 cells the L1CAM expression was upregulated and matrigel invasion was increased after stimulation with TGF-beta1. In L1CAM-positive SK-LU-1 and SK-LC-LL cells matrigel invasion was decreased after L1CAM siRNA knockdown.

Conclusions: A subset of NSCLCs with vessel tropism and increased metastasis aberrantly expresses L1CAM. L1CAM is a novel prognostic marker for NSCLCs that is upregulated by EMT induction and appears to be instrumental for enhanced cell invasion.

Show MeSH
Related in: MedlinePlus