Single-Cell RNA Sequencing Identifies Extracellular Matrix Gene Expression by Pancreatic Circulating Tumor Cells
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, isolati...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-09-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714007050 |
| _version_ | 1818543224425283584 |
|---|---|
| author | David T. Ting Ben S. Wittner Matteo Ligorio Nicole Vincent Jordan Ajay M. Shah David T. Miyamoto Nicola Aceto Francesca Bersani Brian W. Brannigan Kristina Xega Jordan C. Ciciliano Huili Zhu Olivia C. MacKenzie Julie Trautwein Kshitij S. Arora Mohammad Shahid Haley L. Ellis Na Qu Nabeel Bardeesy Miguel N. Rivera Vikram Deshpande Cristina R. Ferrone Ravi Kapur Sridhar Ramaswamy Toshi Shioda Mehmet Toner Shyamala Maheswaran Daniel A. Haber |
| author_facet | David T. Ting Ben S. Wittner Matteo Ligorio Nicole Vincent Jordan Ajay M. Shah David T. Miyamoto Nicola Aceto Francesca Bersani Brian W. Brannigan Kristina Xega Jordan C. Ciciliano Huili Zhu Olivia C. MacKenzie Julie Trautwein Kshitij S. Arora Mohammad Shahid Haley L. Ellis Na Qu Nabeel Bardeesy Miguel N. Rivera Vikram Deshpande Cristina R. Ferrone Ravi Kapur Sridhar Ramaswamy Toshi Shioda Mehmet Toner Shyamala Maheswaran Daniel A. Haber |
| author_sort | David T. Ting |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T22:32:32Z |
| format | Article |
| id | doaj.art-f5cf1b8ba84846e2813882d89a5bd95d |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T22:32:32Z |
| publishDate | 2014-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-f5cf1b8ba84846e2813882d89a5bd95d2022-12-22T00:48:05ZengElsevierCell Reports2211-12472014-09-01861905191810.1016/j.celrep.2014.08.029Single-Cell RNA Sequencing Identifies Extracellular Matrix Gene Expression by Pancreatic Circulating Tumor CellsDavid T. Ting0Ben S. Wittner1Matteo Ligorio2Nicole Vincent Jordan3Ajay M. Shah4David T. Miyamoto5Nicola Aceto6Francesca Bersani7Brian W. Brannigan8Kristina Xega9Jordan C. Ciciliano10Huili Zhu11Olivia C. MacKenzie12Julie Trautwein13Kshitij S. Arora14Mohammad Shahid15Haley L. Ellis16Na Qu17Nabeel Bardeesy18Miguel N. Rivera19Vikram Deshpande20Cristina R. Ferrone21Ravi Kapur22Sridhar Ramaswamy23Toshi Shioda24Mehmet Toner25Shyamala Maheswaran26Daniel A. Haber27Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USACenter for Engineering in Medicine, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USACenter for Engineering in Medicine, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USACenter for Engineering in Medicine, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USAMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USACirculating 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.http://www.sciencedirect.com/science/article/pii/S2211124714007050 |
| spellingShingle | David T. Ting Ben S. Wittner Matteo Ligorio Nicole Vincent Jordan Ajay M. Shah David T. Miyamoto Nicola Aceto Francesca Bersani Brian W. Brannigan Kristina Xega Jordan C. Ciciliano Huili Zhu Olivia C. MacKenzie Julie Trautwein Kshitij S. Arora Mohammad Shahid Haley L. Ellis Na Qu Nabeel Bardeesy Miguel N. Rivera Vikram Deshpande Cristina R. Ferrone Ravi Kapur Sridhar Ramaswamy Toshi Shioda Mehmet Toner Shyamala Maheswaran Daniel A. Haber Single-Cell RNA Sequencing Identifies Extracellular Matrix Gene Expression by Pancreatic Circulating Tumor Cells Cell Reports |
| title | Single-Cell RNA Sequencing Identifies Extracellular Matrix Gene Expression by Pancreatic Circulating Tumor Cells |
| title_full | Single-Cell RNA Sequencing Identifies Extracellular Matrix Gene Expression by Pancreatic Circulating Tumor Cells |
| title_fullStr | Single-Cell RNA Sequencing Identifies Extracellular Matrix Gene Expression by Pancreatic Circulating Tumor Cells |
| title_full_unstemmed | Single-Cell RNA Sequencing Identifies Extracellular Matrix Gene Expression by Pancreatic Circulating Tumor Cells |
| title_short | Single-Cell RNA Sequencing Identifies Extracellular Matrix Gene Expression by Pancreatic Circulating Tumor Cells |
| title_sort | single cell rna sequencing identifies extracellular matrix gene expression by pancreatic circulating tumor cells |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714007050 |
| work_keys_str_mv | AT davidtting singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT benswittner singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT matteoligorio singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT nicolevincentjordan singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT ajaymshah singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT davidtmiyamoto singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT nicolaaceto singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT francescabersani singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT brianwbrannigan singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT kristinaxega singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT jordancciciliano singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT huilizhu singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT oliviacmackenzie singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT julietrautwein singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT kshitijsarora singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT mohammadshahid singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT haleylellis singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT naqu singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT nabeelbardeesy singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT miguelnrivera singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT vikramdeshpande singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT cristinarferrone singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT ravikapur singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT sridharramaswamy singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT toshishioda singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT mehmettoner singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT shyamalamaheswaran singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells AT danielahaber singlecellrnasequencingidentifiesextracellularmatrixgeneexpressionbypancreaticcirculatingtumorcells |