Single-cell RNA sequencing identifies extracellular matrix gene expression by pancreatic circulating tumor cells
Autor: | Vikram Deshpande, Kshitij S. Arora, Olivia C. MacKenzie, Haley Ellis, Miguel Rivera, Daniel A. Haber, Huili Zhu, David T. Miyamoto, Mohammad Shahid, Sridhar Ramaswamy, Ben S. Wittner, Jordan C. Ciciliano, Francesca Bersani, Matteo Ligorio, Ajay Shah, David T. Ting, Ravi Kapur, Toshi Shioda, Shyamala Maheswaran, Kristina Xega, Cristina R. Ferrone, Brian W. Brannigan, Nabeel Bardeesy, Mehmet Toner, Nicole Vincent Jordan, Na Qu, Julie Trautwein, Nicola Aceto |
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Rok vydání: | 2014 |
Předmět: |
Stromal cell
Biology General Biochemistry Genetics and Molecular Biology Article Aldehyde Dehydrogenase 1 Family 03 medical and health sciences Mice 0302 clinical medicine Circulating tumor cell Cell Movement Pancreatic cancer Gene expression medicine Tumor Cells Cultured Animals Humans Osteonectin RNA Small Interfering lcsh:QH301-705.5 030304 developmental biology Regulation of gene expression 0303 health sciences Gene knockdown Sequence Analysis RNA Cancer Retinal Dehydrogenase medicine.disease Neoplastic Cells Circulating Molecular biology Extracellular Matrix Gene Expression Regulation Neoplastic Pancreatic Neoplasms lcsh:Biology (General) 030220 oncology & carcinogenesis Cancer cell Cancer research RNA Interference Carrier Proteins |
Zdroj: | Cell reports Cell Reports, Vol 8, Iss 6, Pp 1905-1918 (2014) Cell Rep |
Popis: | SUMMARY 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. |
Databáze: | OpenAIRE |
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