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Nat Commun. 2017 May 12;8:15078. doi: 10.1038/ncomms15078.

Image-guided genomics of phenotypically heterogeneous populations reveals vascular signalling during symbiotic collective cancer invasion.

Author information

1
Graduate Program in Cancer Biology, Emory University, 1365C Clifton Road, Atlanta, Georgia 30322, USA.
2
Winship Cancer Institute, Emory University, 1365C Clifton Road, Atlanta, Georgia 30322, USA.
3
Department of Chemistry, Emory University, 506 Atwood Drive, Atlanta, Georgia 30322, USA.
4
Department of Biomedical Informatics, Emory University, 36 Eagle Row, Atlanta, Georgia 30322, USA.
5
Department of Biomedical Informatics, Stony Brook University, Stony Brook, New York 11794, USA.
6
Department of Hematology and Medical Oncology, Emory University, 1365C Clifton Road, Atlanta, Georgia 30322, USA.
7
Department of Radiation Oncology, Emory University, 1365C Clifton Road, Atlanta, Georgia 30322, USA.
8
Department of Biostatistics and Bioinformatics, Emory University, 1365C Clifton Road, Atlanta, Georgia 30322, USA.

Abstract

Phenotypic heterogeneity is widely observed in cancer cell populations. Here, to probe this heterogeneity, we developed an image-guided genomics technique termed spatiotemporal genomic and cellular analysis (SaGA) that allows for precise selection and amplification of living and rare cells. SaGA was used on collectively invading 3D cancer cell packs to create purified leader and follower cell lines. The leader cell cultures are phenotypically stable and highly invasive in contrast to follower cultures, which show phenotypic plasticity over time and minimally invade in a sheet-like pattern. Genomic and molecular interrogation reveals an atypical VEGF-based vasculogenesis signalling that facilitates recruitment of follower cells but not for leader cell motility itself, which instead utilizes focal adhesion kinase-fibronectin signalling. While leader cells provide an escape mechanism for followers, follower cells in turn provide leaders with increased growth and survival. These data support a symbiotic model of collective invasion where phenotypically distinct cell types cooperate to promote their escape.

PMID:
28497793
PMCID:
PMC5437311
DOI:
10.1038/ncomms15078
[Indexed for MEDLINE]
Free PMC Article

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