Paracrine signaling between tumor subclones of mouse SCLC: a critical role of ETS transcription factor Pea3 in facilitating metastasis.

Abstract

Tumor heterogeneity can create a unique symbiotic tumor microenvironment. Earlier, we showed that clonal evolution in mouse small cell lung cancer (SCLC) can result in subclones that, upon cografting, endow the neuroendocrine tumor cells with metastatic potential. We now show that paracrine signaling between SCLC subclones is a critical requirement in the early steps of the metastatic process, such as local invasion and intravasation. We further show evidence that paracrine signaling via fibroblast growth factor 2 (Fgf2) and Mapk between these diverged tumor subclones causes enhanced expression of the Pea3 (polyomavirus enhancer activator 3) transcription factor, resulting in metastatic dissemination of the neuroendocrine tumor subclones. Our data reveal for the first time paracrine signaling between tumor cell subclones in SCLC that results in metastatic spread of SCLC.

• Authors: Min-chul Kwon, Natalie Proost, Ji-Ying Song, Kate D Sutherland, John Zevenhoven, Anton Berns
• Journal: Genes & development (Genes Dev) Vol. 29 Issue 15 Pg. 1587-92 (Aug 01 2015) ISSN: 1549-5477 [Electronic] United States
• PMID: 26215568 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Kwon et al.; Published by Cold Spring Harbor Laboratory Press.

Chemical References

• Culture Media, Conditioned
• Proto-Oncogene Proteins c-ets
• Transcription Factors
• transcription factor PEA3
• Fibroblast Growth Factor 2
• Mitogen-Activated Protein Kinase 1

Topics

• Animals
• Cell Line, Tumor
• Culture Media, Conditioned
• Fibroblast Growth Factor 2 (metabolism)
• Gene Expression Regulation, Neoplastic (genetics)
• Gene Knockdown Techniques
• Mice
• Mice, Inbred BALB C
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Neoplasm Invasiveness (genetics)
• Neoplasm Metastasis (genetics, physiopathology)
• Paracrine Communication (physiology)
• Proto-Oncogene Proteins c-ets (genetics, metabolism)
• Small Cell Lung Carcinoma (physiopathology)
• Transcription Factors (genetics, metabolism)