Single-cell RNA sequencing identifies extracellular matrix gene expression by pancreatic circulating tumor cells

Cell Rep. 2014 Sep 25;8(6):1905-1918. doi: 10.1016/j.celrep.2014.08.029. Epub 2014 Sep 18.


Circulating tumor cells (CTCs) are shed from primary tumors into the bloodstream, mediating the hematogenous spread of cancer to distant organs. To define their composition, we compared genome-wide expression profiles of CTCs with matched primary tumors in a mouse model of pancreatic cancer, isolating individual CTCs using epitope-independent microfluidic capture, followed by single-cell RNA sequencing. CTCs clustered separately from primary tumors and tumor-derived cell lines, showing low-proliferative signatures, enrichment for the stem-cell-associated gene Aldh1a2, biphenotypic expression of epithelial and mesenchymal markers, and expression of Igfbp5, a gene transcript enriched at the epithelial-stromal interface. Mouse as well as human pancreatic CTCs exhibit a very high expression of stromal-derived extracellular matrix (ECM) proteins, including SPARC, whose knockdown in cancer cells suppresses cell migration and invasiveness. The aberrant expression by CTCs of stromal ECM genes points to their contribution of microenvironmental signals for the spread of cancer to distant organs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Dehydrogenase 1 Family
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Movement
  • Extracellular Matrix / genetics*
  • Extracellular Matrix / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice
  • Neoplastic Cells, Circulating / metabolism*
  • Osteonectin / antagonists & inhibitors
  • Osteonectin / genetics
  • Osteonectin / metabolism
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Retinal Dehydrogenase / genetics
  • Retinal Dehydrogenase / metabolism
  • Sequence Analysis, RNA
  • Tumor Cells, Cultured


  • Carrier Proteins
  • IGFBP5-interacting protein, human
  • Osteonectin
  • RNA, Small Interfering
  • Aldehyde Dehydrogenase 1 Family
  • ALDH1A2 protein, human
  • Retinal Dehydrogenase

Associated data

  • GEO/GSE51372
  • GEO/GSE51827
  • GEO/GSE60407