Usage Information
Abstract
Small cell lung cancer (SCLC) is the most aggressive lung cancer entity with an extremely limited therapeutic outcome. Most patients are diagnosed at an extensive stage. However, the molecular mechanisms driving SCLC invasion and metastasis remain largely elusive. We used an autochthonous SCLC mouse model and matched samples from patients with primary and metastatic SCLC to investigate the molecular characteristics of tumor metastasis. We demonstrate that tumor cell invasion and liver metastasis in SCLC are triggered by an Angiopoietin-2 (ANG-2)/Integrin β-1–dependent pathway in tumor cells, mediated by focal adhesion kinase/Src kinase signaling. Strikingly, CRISPR-Cas9 KO of Integrin β-1 or blocking Integrin β-1 signaling by an anti–ANG-2 treatment abrogates liver metastasis formation in vivo. Interestingly, analysis of a unique collection of matched samples from patients with primary and metastatic SCLC confirmed a strong increase of Integrin β-1 in liver metastasis in comparison with the primary tumor. We further show that ANG-2 blockade combined with PD-1–targeted by anti-PD-1 treatment displays synergistic treatment effects in SCLC. Together, our data demonstrate a fundamental role of ANG-2/Integrin β-1 signaling in SCLC cells for tumor cell invasion and liver metastasis and provide a potentially new effective treatment strategy for patients with SCLC.
Authors
Lydia Meder, Charlotte Isabelle Orschel, Christoph Julius Otto, Mirjam Koker, Johannes Brägelmann, Meryem S. Ercanoglu, Sabrina Dähling, Anik Compes, Carolin Selenz, Marieke Nill, Felix Dietlein, Alexandra Florin, Marie-Lisa Eich, Sven Borchmann, Margarete Odenthal, Raquel Blazquez, Frank Hilberg, Florian Klein, Michael Hallek, Reinhard Büttner, H. Christian Reinhardt, Roland T. Ullrich
Usage data is cumulative from January 2025 through January 2026.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 1,601 | 513 |
| 243 | 74 | |
| Figure | 1,352 | 28 |
| Supplemental data | 1,064 | 24 |
| Citation downloads | 85 | 0 |
| Totals | 4,345 | 639 |
| Total Views | 4,984 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
