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Inducible expression of tissue factor in small-cell lung cancer: impact on morphology and matrix metalloproteinase secretion

Abstract

Purpose

Tissue factor (TF), the transmembrane receptor for factor VIIa (FVIIa), has key regulatory functions in coagulation as well as in tumour progression and metastasis. Small-cell lung cancer (SCLC) metastasises more aggressively than non-small-cell lung cancer (NSCLC). Previously, we described the transition of SCLC cell line H69 to adherent growth and TF expression. Here, we explored the differential expression of TF and its functional impact on morphology and matrix metalloproteinase (MMP) secretion.

Methods

The constitutional TF expression was evaluated in a panel of established NSCLC and SCLC cell lines. Furthermore, in three stress-selected adherent SCLC H69 cells, TF and MMP expressions were determined by mRNA, protein, and activity measurements. RNA interference-mediated TF down-regulation and FVIIa stimulation were used to study the impact of TF on cellular functions.

Results

NSCLC cells expressed high TF antigen (median 3.75 ng/mg; range 0.31–65.2 ng/mg protein, n = 8), while SCLC expressed none or low TF (median 0.07 ng/mg; range 0–0.39 ng/mg protein, n = 6). However, selected H69 adherent cells markedly expressed TF (range: 4.8–44.3 ng/mg protein, n = 3) and secreted MMP-2 and MMP-9. FVIIa stimulated MMP-2 and MMP-9 secretion in H69adh cells, whereas TF down-regulation diminished MMP-2 and MMP-9 expression and promoted reversion to suspension growth.

Conclusions

Our data show the significance of TF expression in the reversible growth phenotype of H69. Because TF, MMP expression, and adherence are highly relevant to cancer metastasis, this study suggests a novel mechanism of adaptation, thereby adding to the understanding of SCLC biology and its aggressiveness.

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Acknowledgments

We are grateful to Annette Rausch-Müller and Salvatore Volpe for excellent technical assistance.

Conflict of interest

We declare that we have no conflict of interest.

Author information

Correspondence to Ursula Salge-Bartels.

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Hahn, N., Heiden, M., Seitz, R. et al. Inducible expression of tissue factor in small-cell lung cancer: impact on morphology and matrix metalloproteinase secretion. J Cancer Res Clin Oncol 138, 695–703 (2012). https://doi.org/10.1007/s00432-011-1139-1

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Keywords

  • Tissue factor
  • Small-cell lung cancer
  • Matrix metalloproteinase
  • Coagulation
  • Small interfering RNA