Single-cell RNAseq uncovers involution mimicry as an aberrant development pathway during breast cancer metastasis

作者: Fatima Valdes-Mora , Robert Salomon , Brian Gloss , Andrew MK. Law , Lesley Castillo

DOI: 10.1101/624890

关键词: CarcinogenesisCancer cellBreast cancerCellBiologyCancer researchMammary glandCancerCell typeInvolution (medicine)

摘要: Abstract Single-cell RNA-seq has emerged as a powerful method to unravel heterogeneity of complex biological systems; this enabled in vivo characterization cell type compositions through unsupervised sampling and modelling transcriptional states single cells. Here we used the high-throughput microfluidic-based single-cell Drop-seq elucidate cellular composition functional diversity breast tumours during induction metastatic disease transgenic model related pregnancy-associated cancer (PABC). We characterised with unprecedented definition, how activation developmental programs associated pregnancy results acquisition an aggressive phenotype. show that cells are classified structure comparable lineages epithelial mammary gland hierarchy, revealing high dynamics plasticity progression. This progression program is orchestrated by alveolar milk secretory cells, conjunction types from tumour microenvironment (TME), including cancer-associated fibroblasts (CAFs), form multi-cellular process resembles aberrant involution. Finally, analysed interactome ecosystem define high-resolution landscape molecular pathways cell-to-cell communication underpins extra-cellular remodelling inflammation involution mimicry. In conclusion, our study recapitulates mechanisms have gone awry carcinogenesis PABC. provide large-scale allows understanding deep analysis key events result malignancy.

参考文章(112)
Umme Amara, Daniel Rittirsch, Michael Flierl, Uwe Bruckner, Andreas Klos, Florian Gebhard, John D. Lambris, Markus Huber-Lang, Interaction between the coagulation and complement system. Advances in Experimental Medicine and Biology. ,vol. 632, pp. 71- 79 ,(2008) , 10.1007/978-0-387-78952-1_6
Robert Möhle, Frank Bautz, Shahin Rafii, Malcolm A.S. Moore, Wolfram Brugger, Lothar Kanz, The Chemokine Receptor CXCR-4 Is Expressed on CD34+Hematopoietic Progenitors and Leukemic Cells and Mediates Transendothelial Migration Induced by Stromal Cell-Derived Factor-1 Blood. ,vol. 91, pp. 4523- 4530 ,(1998) , 10.1182/BLOOD.V91.12.4523
Anna Fantozzi, Gerhard Christofori, Mouse models of breast cancer metastasis Breast Cancer Research. ,vol. 8, pp. 212- 212 ,(2006) , 10.1186/BCR1530
Monica M Richert, Kathryn L Schwertfeger, John W Ryder, Steven M Anderson, An Atlas of Mouse Mammary Gland Development Journal of Mammary Gland Biology and Neoplasia. ,vol. 5, pp. 227- 241 ,(2000) , 10.1023/A:1026499523505
Karin E de Visser, Metamia Ciampricotti, Ewa M Michalak, David Wei-Min Tan, Ewoud N Speksnijder, Cheei-Sing Hau, Hans Clevers, Nick Barker, Jos Jonkers, Developmental stage-specific contribution of LGR5(+) cells to basal and luminal epithelial lineages in the postnatal mammary gland. The Journal of Pathology. ,vol. 228, pp. 300- 309 ,(2012) , 10.1002/PATH.4096
Torsten Stein, Joanna S Morris, Claire R Davies, Stephen J Weber-Hall, Marie-Anne Duffy, Victoria J Heath, Alexandra K Bell, Roderick K Ferrier, Gavin P Sandilands, Barry A Gusterson, Involution of the mouse mammary gland is associated with an immune cascade and an acute-phase response, involving LBP, CD14 and STAT3 Breast Cancer Research. ,vol. 6, pp. 1- 17 ,(2004) , 10.1186/BCR753
Holly A. Martinson, Sonali Jindal, Clarissa Durand‐Rougely, Virginia F. Borges, Pepper Schedin, Wound healing-like immune program facilitates postpartum mammary gland involution and tumor progression. International Journal of Cancer. ,vol. 136, pp. 1803- 1813 ,(2015) , 10.1002/IJC.29181
Giovanni Ciriello, Michael L Gatza, Andrew H Beck, Matthew D Wilkerson, Suhn K Rhie, Alessandro Pastore, Hailei Zhang, Michael McLellan, Christina Yau, Cyriac Kandoth, Reanne Bowlby, Hui Shen, Sikander Hayat, Robert Fieldhouse, Susan C Lester, MK Gary, Rachel E Factor, Laura C Collins, Kimberly H Allison, Yunn-Yi Chen, Kristin Jensen, Nicole B Johnson, Steffi Oesterreich, Gordon B Mills, Andrew D Cherniack, Gordon Robertson, Christopher Benz, Chris Sander, Peter W Laird, Katherine A Hoadley, Tari A King, Rehan Akbani, J Todd Auman, Miruna Balasundaram, Saianand Balu, Thomas Barr, Andrew Beck, Stephen Benz, Mario Berrios, Rameen Beroukhim, Tom Bodenheimer, Lori Boice, Moiz S Bootwalla, Jay Bowen, Denise Brooks, Lynda Chin, Juok Cho, Sudha Chudamani, Tanja Davidsen, John A Demchok, Jennifer B Dennison, Li Ding, Ina Felau, Martin L Ferguson, Scott Frazer, Stacey B Gabriel, JianJiong Gao, Julie M Gastier-Foster, Nils Gehlenborg, Mark Gerken, Gad Getz, William J Gibson, D Neil Hayes, David I Heiman, Andrea Holbrook, Robert A Holt, Alan P Hoyle, Hai Hu, Mei Huang, Carolyn M Hutter, E Shelley Hwang, Stuart R Jefferys, Steven JM Jones, Zhenlin Ju, Jaegil Kim, Phillip H Lai, Michael S Lawrence, Kristen M Leraas, Tara M Lichtenberg, Pei Lin, Shiyun Ling, Jia Liu, Wenbin Liu, Laxmi Lolla, Yiling Lu, Yussanne Ma, Dennis T Maglinte, Elaine Mardis, Jeffrey Marks, Marco A Marra, Cynthia McAllister, Shaowu Meng, Matthew Meyerson, Richard A Moore, Lisle E Mose, Andrew J Mungall, Bradley A Murray, Rashi Naresh, Michael S Noble, Olufunmilayo Olopade, Joel S Parker, Charles M Perou, Todd Pihl, Gordon Saksena, Steven E Schumacher, Kenna R Mills Shaw, Nilsa C Ramirez, W Kimryn Rathmell, Jeffrey Roach, A Gordon Robertson, Jacqueline E Schein, Nikolaus Schultz, Margi Sheth, Yan Shi, Juliann Shih, Carl Simon Shelley, Craig Shriver, Janae V Simons, Heidi J Sofia, Matthew G Soloway, Carrie Sougnez, Charlie Sun, Roy Tarnuzzer, Daniel G Tiezzi, David J Van Den Berg, Doug Voet, Yunhu Wan, Zhining Wang, John N Weinstein, Daniel J Weisenberger, Richard Wilson, Lisa Wise, Maciej Wiznerowicz, Junyuan Wu, Ye Wu, Liming Yang, Travis I Zack, Jean C Zenklusen, Jiashan Zhang, Erik Zmuda, None, Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer. Cell. ,vol. 163, pp. 506- 519 ,(2015) , 10.1016/J.CELL.2015.09.033