Dissecting phenotypic transitions in metastatic disease via photoconversion-based isolation

Elife. 2021 Feb 23:10:e63270. doi: 10.7554/eLife.63270.

Abstract

Cancer patients often harbor occult metastases, a potential source of relapse that is targetable only through systemic therapy. Studies of this occult fraction have been limited by a lack of tools with which to isolate discrete cells on spatial grounds. We developed PIC-IT, a photoconversion-based isolation technique allowing efficient recovery of cell clusters of any size - including single-metastatic cells - which are largely inaccessible otherwise. In a murine pancreatic cancer model, transcriptional profiling of spontaneously arising microcolonies revealed phenotypic heterogeneity, functionally reduced propensity to proliferate and enrichment for an inflammatory-response phenotype associated with NF-κB/AP-1 signaling. Pharmacological inhibition of NF-κB depleted microcolonies but had no effect on macrometastases, suggesting microcolonies are particularly dependent on this pathway. PIC-IT thus enables systematic investigation of metastatic heterogeneity. Moreover, the technique can be applied to other biological systems in which isolation and characterization of spatially distinct cell populations is not currently feasible.

Keywords: cancer biology; cell isolation; metastasis; mouse; photoconversion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Disease Models, Animal
  • Female
  • Gene Expression Profiling*
  • Light
  • Male
  • Medical Oncology / methods*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Metastasis / diagnosis*
  • Pancreatic Neoplasms / physiopathology*
  • Phenotype*
  • Photochemical Processes

Associated data

  • GEO/GSE158078