Limits...
Selectins mediate small cell lung cancer systemic metastasis.

Heidemann F, Schildt A, Schmid K, Bruns OT, Riecken K, Jung C, Ittrich H, Wicklein D, Reimer R, Fehse B, Heeren J, Lüers G, Schumacher U, Heine M - PLoS ONE (2014)

Bottom Line: Accordingly, formation of spontaneous distant metastases was reduced by 50% when OH-1 cells were xenografted into E-/P-selectin-deficient mice compared with wild type mice (p = 0.0181).However, as metastasis formation was not completely abrogated in selectin deficient mice, we concluded that this adhesion cascade is redundant and that other molecules of this cascade mediate metastasis formation as well.Using several of these adhesion molecules as interaction partners presumably make SCLC cells so highly metastatic.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Experimental Morphology, University Medical Center Hamburg- Eppendorf, Hamburg, Germany.

ABSTRACT
Metastasis formation is the major reason for the extremely poor prognosis in small cell lung cancer (SCLC) patients. The molecular interaction partners regulating metastasis formation in SCLC are largely unidentified, however, from other tumor entities it is known that tumor cells use the adhesion molecules of the leukocyte adhesion cascade to attach to the endothelium at the site of the future metastasis. Using the human OH-1 SCLC line as a model, we found that these cells expressed E- and P-selectin binding sites, which could be in part attributed to the selectin binding carbohydrate motif sialyl Lewis A. In addition, protein backbones known to carry these glycotopes in other cell lines including PSGL-1, CD44 and CEA could be detected in in vitro and in vivo grown OH1 SCLC cells. By intravital microscopy of murine mesenterial vasculature we could capture SCLC cells while rolling along vessel walls demonstrating that SCLC cells mimic leukocyte rolling behavior in terms of selectin and selectin ligand interaction in vivo indicating that this mechanism might indeed be important for SCLC cells to seed distant metastases. Accordingly, formation of spontaneous distant metastases was reduced by 50% when OH-1 cells were xenografted into E-/P-selectin-deficient mice compared with wild type mice (p = 0.0181). However, as metastasis formation was not completely abrogated in selectin deficient mice, we concluded that this adhesion cascade is redundant and that other molecules of this cascade mediate metastasis formation as well. Using several of these adhesion molecules as interaction partners presumably make SCLC cells so highly metastatic.

Show MeSH

Related in: MedlinePlus

OH-1-LUC/mCherry cells grown in vivo are CEA and E-/P- selectin binding positive.Isolated OH-1-LUC/mCherry cells of primary tumors were stained in parallel against CEA and E- or P-selectin binding and FACS analyzed. (A) OH-1-LUC/mCherry cells showed no binding to isotype and FC-chimaera controls. (B) Almost all cells were CEA and E-selectin binding positive, by contrast (C) two thirds of the cells were P-selectin binding negative. Isotype controls are shown as dotted lines.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3974710&req=5

pone-0092327-g002: OH-1-LUC/mCherry cells grown in vivo are CEA and E-/P- selectin binding positive.Isolated OH-1-LUC/mCherry cells of primary tumors were stained in parallel against CEA and E- or P-selectin binding and FACS analyzed. (A) OH-1-LUC/mCherry cells showed no binding to isotype and FC-chimaera controls. (B) Almost all cells were CEA and E-selectin binding positive, by contrast (C) two thirds of the cells were P-selectin binding negative. Isotype controls are shown as dotted lines.

Mentions: By use of FACS analysis (Fig. 2) we investigated whether in vivo grown OH-1 cells of primary xenografted tumors have maintained the ability to bind to selectins fusion proteins. Cells harvested from primary OH-1-LUC/mCherry tumors were double labelled with anti-CEA and a human E- or P-selectin chimaera. Almost all cells (78%) were both positive for anti-CEA staining and E-selectin binding (Fig. 2). Double staining of anti-CEA and human P-selectin chimaera revealed that 36% of the cells were both positive for P-selectin binding and CEA (Fig. 2C).


Selectins mediate small cell lung cancer systemic metastasis.

Heidemann F, Schildt A, Schmid K, Bruns OT, Riecken K, Jung C, Ittrich H, Wicklein D, Reimer R, Fehse B, Heeren J, Lüers G, Schumacher U, Heine M - PLoS ONE (2014)

OH-1-LUC/mCherry cells grown in vivo are CEA and E-/P- selectin binding positive.Isolated OH-1-LUC/mCherry cells of primary tumors were stained in parallel against CEA and E- or P-selectin binding and FACS analyzed. (A) OH-1-LUC/mCherry cells showed no binding to isotype and FC-chimaera controls. (B) Almost all cells were CEA and E-selectin binding positive, by contrast (C) two thirds of the cells were P-selectin binding negative. Isotype controls are shown as dotted lines.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3974710&req=5

pone-0092327-g002: OH-1-LUC/mCherry cells grown in vivo are CEA and E-/P- selectin binding positive.Isolated OH-1-LUC/mCherry cells of primary tumors were stained in parallel against CEA and E- or P-selectin binding and FACS analyzed. (A) OH-1-LUC/mCherry cells showed no binding to isotype and FC-chimaera controls. (B) Almost all cells were CEA and E-selectin binding positive, by contrast (C) two thirds of the cells were P-selectin binding negative. Isotype controls are shown as dotted lines.
Mentions: By use of FACS analysis (Fig. 2) we investigated whether in vivo grown OH-1 cells of primary xenografted tumors have maintained the ability to bind to selectins fusion proteins. Cells harvested from primary OH-1-LUC/mCherry tumors were double labelled with anti-CEA and a human E- or P-selectin chimaera. Almost all cells (78%) were both positive for anti-CEA staining and E-selectin binding (Fig. 2). Double staining of anti-CEA and human P-selectin chimaera revealed that 36% of the cells were both positive for P-selectin binding and CEA (Fig. 2C).

Bottom Line: Accordingly, formation of spontaneous distant metastases was reduced by 50% when OH-1 cells were xenografted into E-/P-selectin-deficient mice compared with wild type mice (p = 0.0181).However, as metastasis formation was not completely abrogated in selectin deficient mice, we concluded that this adhesion cascade is redundant and that other molecules of this cascade mediate metastasis formation as well.Using several of these adhesion molecules as interaction partners presumably make SCLC cells so highly metastatic.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Experimental Morphology, University Medical Center Hamburg- Eppendorf, Hamburg, Germany.

ABSTRACT
Metastasis formation is the major reason for the extremely poor prognosis in small cell lung cancer (SCLC) patients. The molecular interaction partners regulating metastasis formation in SCLC are largely unidentified, however, from other tumor entities it is known that tumor cells use the adhesion molecules of the leukocyte adhesion cascade to attach to the endothelium at the site of the future metastasis. Using the human OH-1 SCLC line as a model, we found that these cells expressed E- and P-selectin binding sites, which could be in part attributed to the selectin binding carbohydrate motif sialyl Lewis A. In addition, protein backbones known to carry these glycotopes in other cell lines including PSGL-1, CD44 and CEA could be detected in in vitro and in vivo grown OH1 SCLC cells. By intravital microscopy of murine mesenterial vasculature we could capture SCLC cells while rolling along vessel walls demonstrating that SCLC cells mimic leukocyte rolling behavior in terms of selectin and selectin ligand interaction in vivo indicating that this mechanism might indeed be important for SCLC cells to seed distant metastases. Accordingly, formation of spontaneous distant metastases was reduced by 50% when OH-1 cells were xenografted into E-/P-selectin-deficient mice compared with wild type mice (p = 0.0181). However, as metastasis formation was not completely abrogated in selectin deficient mice, we concluded that this adhesion cascade is redundant and that other molecules of this cascade mediate metastasis formation as well. Using several of these adhesion molecules as interaction partners presumably make SCLC cells so highly metastatic.

Show MeSH
Related in: MedlinePlus