TY - JOUR
T1 - Single-cell RNA sequencing identifies extracellular matrix gene expression by pancreatic circulating tumor cells
AU - Ting, David T.
AU - Wittner, Ben S.
AU - Ligorio, Matteo
AU - Vincent Jordan, Nicole
AU - Shah, Ajay M.
AU - Miyamoto, David T.
AU - Aceto, Nicola
AU - Bersani, Francesca
AU - Brannigan, Brian W.
AU - Xega, Kristina
AU - Ciciliano, Jordan C.
AU - Zhu, Huili
AU - MacKenzie, Olivia C.
AU - Trautwein, Julie
AU - Arora, Kshitij S.
AU - Shahid, Mohammad
AU - Ellis, Haley L.
AU - Qu, Na
AU - Bardeesy, Nabeel
AU - Rivera, Miguel N.
AU - Deshpande, Vikram
AU - Ferrone, Cristina R.
AU - Kapur, Ravi
AU - Ramaswamy, Sridhar
AU - Shioda, Toshi
AU - Toner, Mehmet
AU - Maheswaran, Shyamala
AU - Haber, Daniel A.
N1 - Funding Information:
We are grateful to Laura Libby for mouse colony care, Lev Silberstein for providing technical assistance in single-cell RNA sequencing, Linda Nieman for microscopy expertise, and engineering techs for their help in running samples on the CTC-iChip. This work was supported by Stand Up to Cancer (D.A.H., M.T., and S.M.), Howard Hughes Medical Institute (D.A.H. and M.N.R.), NIBIB Quantum grant 5R01EB008047 (M.T.), NCI 2R01CA129933 (D.A.H.), National Foundation for Cancer Research (D.A.H.), the Burroughs Wellcome Fund (D.T.T. and M.N.R.), K12CA087723-11A1 (D.T.T.), Department of Defense (D.T.M. and D.T.T.), Affymetrix, Inc. (D.T.T., M.N.R., and V.D.), the Warshaw Institute for Pancreatic Cancer Research (D.T.T.), and the Verville Family Pancreatic Cancer Research Fund (D.T.T.).
Publisher Copyright:
© 2014 The Authors.
PY - 2014/9/25
Y1 - 2014/9/25
N2 - 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.
AB - 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.
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U2 - 10.1016/j.celrep.2014.08.029
DO - 10.1016/j.celrep.2014.08.029
M3 - Article
C2 - 25242334
AN - SCOPUS:84907414338
SN - 2211-1247
VL - 8
SP - 1905
EP - 1918
JO - Cell Reports
JF - Cell Reports
IS - 6
ER -