Clones of Tumor Cells Derived from a Single Primary Human Lung Tumor Reveal Different Patterns of β<sub>1</sub>Integrin Expression

Chen, Fang-An; Alosco, Thomas; Croy, B A; Narumi, Kunihiro; Percy, D. H.; Bankert, Richard B.

doi:10.3109/15419069409014209

Cited by 23 publications

(12 citation statements)

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“…The presence of cytokines and growth factors at sites where cancer cells eventually reside may have direct impact on the outcome of tumor metastasis. It has been shown that the metastatic potential of melanoma, osteosarcoma, rhabdomyosarcoma, and lung tumors correlated with increases in ␣2␤1 expression; whereas, decreases in ␣2␤1 expression has been associated with epithelial malignant transformation (Dedhar and Saulnier, 1990;Chan et al, 1991;Klein et al, 1991;Mortarini et al, 1991;Pignatelli et al, 1991;Danen et al, 1993;Chen et al, 1994;Santala et al, 1994;Zutter et al, 1995). Our current work and our recent studies of RD cells may explain why both an enhancing and inhibitory effect of ␣2␤1 on tumor metastasis have been reported.…”

Section: Discussionmentioning

confidence: 56%

“…In addition, ␣2␤1 has also been associated with the metastatic activities of tumor cells. Interestingly, there is both a direct correlation (Dedhar and Saulnier, 1990;Chan et al, 1991;Klein et al, 1991;Mortarini et al, 1991;Danen et al, 1993;Chen et al, 1994;Santala et al, 1994) and an inverse correlation (Pignatelli et al, 1990(Pignatelli et al, , 1991Zutter, et al, 1990Zutter, et al, , 1995 of ␣2␤1 expression with tumor metastasis. The exact mechanisms whereby ␣2␤1 enhances or, in some cases, reduces the metastatic activities of tumor cells are still unclear.…”

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confidence: 99%

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Modulation of In Vivo Migratory Function of α2β1 Integrin in Mouse Liver

Heinemann

Hangan

et al. 1997

MBoC

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We report herein that expression of ␣2␤1 integrin increased human erythroleukemia K562 transfectant (KX2C2) cell movement after extravasation into liver parenchyma. In contrast, a previous study demonstrated that ␣2␤1 expression conferred a stationary phenotype to human rhabdomyosarcoma RD transfectant (RDX2C2) cells after extravasation into the liver. We therefore assessed the adhesive and migratory function of ␣2␤1 on KX2C2 and RDX2C2 cells using a ␣2␤1-specific stimulatory monoclonal antibody (mAb), JBS2, and a blocking mAb, BHA2.1. In comparison with RDX2C2 cells, KX2C2 were only weakly adherent to collagen and laminin. JBS2 stimulated ␣2␤1-mediated interaction of KX2C2 cells with both collagen and laminin resulting in increases in cell movement on both matrix proteins. In the presence of Mn 2ϩ , JBS2-stimulated adhesion on collagen beyond an optimal level for cell movement. In comparison, an increase in RDX2C2 cell movement on collagen required a reduction in its adhesive strength provided by the blocking mAb BHA2.1. Consistent with these in vitro findings, in vivo videomicroscopy revealed that ␣2␤1-mediated postextravasation cell movement of KX2C2 cells in the liver tissue could also be stimulated by JBS2. Thus, results demonstrate that ␣2␤1 expression can modulate postextravasation cell movement by conferring either a stationary or motile phenotype to different cell types. These findings may be related to the differing metastatic activities of different tumor cell types. INTRODUCTIONIt is well established that ␤1 integrins represent the major receptors for providing the functional linkage between extracellular matrix (ECM) proteins and cytoskeletal components (for review, Hynes, 1992). The expression of ␣2␤1 integrin as receptors for collagen and laminin has been associated with the morphogenesis of mammary epithelial cells (Berdichevsky et al., 1992; Keely et al., 1995a,b) and differentiation of the human erythroleukemia cell line K562 (Burger et al., 1992). In comparison, ␣2␤1 expression was down-regulated on keratinocytes undergoing terminal differentiation (Adams and Watt, 1990). In addition, ␣2␤1 has also been associated with the metastatic activities of tumor cells. Interestingly, there is both a direct correlation (Dedhar and Saulnier, 1990;Chan et al., 1991;Klein et al., 1991;Mortarini et al., 1991;Danen et al., 1993;Chen et al., 1994;Santala et al., 1994) and an inverse correlation (Pignatelli et al., 1990(Pignatelli et al., , 1991Zutter, et al., 1990Zutter, et al., , 1995 of ␣2␤1 expression with tumor metastasis. The exact mechanisms whereby ␣2␤1 enhances or, in some cases, reduces the metastatic activities of tumor cells are still unclear. One possibility is that ␣2␤1 may confer distinct cell functions among the tumor cells. The present study focuses on ␣2␤1 interaction with ECM proteins and its in vivo effect on cell movement.Studies in recent years have demonstrated three distinct modes of ligand binding for ␣2␤1: no ligandbinding activity, binding collagen but not laminin, and binding both ...

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Section: Discussionmentioning

confidence: 56%

mentioning

confidence: 99%

Modulation of In Vivo Migratory Function of α2β1 Integrin in Mouse Liver

Heinemann

Hangan

et al. 1997

MBoC

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“…Furthermore, increased expression of ␣ 2 ␤ 1 has been shown to be positively correlated with increased metastatic ability in human NSCLC cells when intravenously inoculated in severe combined immunodefi ciency mice, suggesting the involvement of ␣ 2 -as well as ␤ 1 -integrins in NSCLC invasion [23] . Based on these observations, it is suggested that CAM may suppress the invasive potential of A549 cells in part through downregulation of the ␣ 2 -and ␤ 1 -integrin expression.…”

Section: Discussionmentioning

confidence: 99%

Clarithromycin Suppresses Invasiveness of Human Lung Adenocarcinoma Cells

Wada

Sata²,

Sato³

et al. 2007

Chemotherapy

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Background: It has been speculated that clarithromycin (CAM), a 14-membered ring macrolide, possesses antitumor effects besides antimicrobial and anti-inflammatory effects. Method: We evaluated the effects of CAM on the growth and invasiveness of A549 lung adenocarcinoma cells. Results: Although CAM did not affect the growth of A549 cells, the Matrigel invasion assay showed that the potential of invasion was diminished by CAM treatment. When analyzed by flow cytometry, CAM suppressed α₂- and β₁-integrin expression. Furthermore, thymidine phosphorylase (TP) expression was diminished by CAM treatment in a dose-dependent manner. A specific TP inhibitor also suppressed β₁-integrin expression in flow cytometric analysis. Conclusions: These results suggest that CAM may suppress invasive activity of A549 cells in part by diminishing the expression of TP, α₂- and β₁-integrin, which may be a downstream signal of the TP pathway, and that CAM could be useful in the treatment of lung adenocarcinoma.

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“…Changes in the expression of integrins have been observed in lung cancers and linked to aggressive tumor behavior. As one example, changes in the expression levels of certain integrin subunits have been correlated with metastatic potential in NSCLC [86,87]. Integrin expression has also been associated with tumor angiogenesis; studies have demonstrated in vitro tumor regression with inhibition of the integrin ␣v␤ 3 [88,89].…”

Section: Novel Agentsmentioning

confidence: 99%

Benefits and limitations of antiangiogenic agents in patients with non-small cell lung cancer

Bertino

2010

Lung Cancer

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Clones of Tumor Cells Derived from a Single Primary Human Lung Tumor Reveal Different Patterns of β₁Integrin Expression

Cited by 23 publications

References 32 publications

Modulation of In Vivo Migratory Function of α2β1 Integrin in Mouse Liver

Modulation of In Vivo Migratory Function of α2β1 Integrin in Mouse Liver

Clarithromycin Suppresses Invasiveness of Human Lung Adenocarcinoma Cells

Benefits and limitations of antiangiogenic agents in patients with non-small cell lung cancer

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Clones of Tumor Cells Derived from a Single Primary Human Lung Tumor Reveal Different Patterns of β1Integrin Expression

Cited by 23 publications

References 32 publications

Modulation of In Vivo Migratory Function of α2β1 Integrin in Mouse Liver

Modulation of In Vivo Migratory Function of α2β1 Integrin in Mouse Liver

Clarithromycin Suppresses Invasiveness of Human Lung Adenocarcinoma Cells

Benefits and limitations of antiangiogenic agents in patients with non-small cell lung cancer

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Clones of Tumor Cells Derived from a Single Primary Human Lung Tumor Reveal Different Patterns of β₁Integrin Expression