@article{46cf27e4fc5d44b4afe90aa4fd62d6e0,
title = "A tumor-derived type III collagen-rich ECM niche regulates tumor cell dormancy",
abstract = "Cancer cells disseminate and seed in distant organs, where they can remain dormant for many years before forming clinically detectable metastases. Here we studied how disseminated tumor cells sense and remodel the extracellular matrix (ECM) to sustain dormancy. ECM proteomics revealed that dormant cancer cells assemble a type III collagen-enriched ECM niche. Tumor-derived type III collagen is required to sustain tumor dormancy, as its disruption restores tumor cell proliferation through DDR1-mediated STAT1 signaling. Second-harmonic generation two-photon microscopy further revealed that the dormancy-to-reactivation transition is accompanied by changes in type III collagen architecture and abundance. Analysis of clinical samples revealed that type III collagen levels were increased in tumors from patients with lymph node-negative head and neck squamous cell carcinoma compared to patients who were positive for lymph node colonization. Our data support the idea that the manipulation of these mechanisms could serve as a barrier to metastasis through disseminated tumor cell dormancy induction.",
author = "{Di Martino}, {Julie S.} and Nobre, {Ana Rita} and Chandrani Mondal and Isra Taha and Farias, {Eduardo F.} and Fertig, {Elana J.} and Alexandra Naba and Aguirre-Ghiso, {Julio A.} and Bravo-Cordero, {Jose Javier}",
note = "Funding Information: J.J.B.-C., E.J.F. and A.N. thank the National Cancer Institute (NCI) and Sage Bionetwork{\textquoteright}s Interdisciplinary Approaches to Cancer Metastasis workshop for inspiring this project. We thank S. Spencer for providing the DHB-Venus plasmid, B. Leitinger for sharing DDR1 plasmids, M. Soengas for the FG12-GFP plasmid, L. Hodgson for providing HEK cells, non-targeting CRISPR controls and lentiviral packaging plasmids, E. Farias for guidance on mouse surgery, M. Djedaini and S. Bekri for guidance on FACS, B. Wu for building the plastic imaging window and J. Cheung for guidance on the CAM model. We acknowledge the Microscopy and Advanced Bioimaging Core and the Flow Cytometry Core at Mount Sinai. We thank J. Gregory for her illustration of the graphical abstract. We thank the Aguirre-Ghiso and Sosa laboratories for helpful discussions. We also thank T. Martin for revising the statistical analysis throughout the paper. We thank H. Chen from the Mass Spectrometry Core facility at the University of Illinois at Chicago and G. Chlipala from the Research Informatics Core facility at the University of Illinois at Chicago for their technical assistance with the analysis of D-HEp3 shCTRL versus D-HEp3 shDDR1 tumors and R. Schiavoni from the Proteomics Core Facility at the Koch Institute for Integrative Cancer Research at MIT and K. Clauser from the Broad Institute for their assistance with the analysis of T-HEp3 and D-HEp3 tumors. This work was supported by a Susan G. Komen Career Catalyst Research award (CCR18547848 to J.J.B.-C.), an NCI Career Transition Award (K22CA196750 to J.J.B.-C.), an NCI R01 grant (R01CA244780 to J.J.B.-C.), the Tisch Cancer Institute National Institutes of Health (NIH) Cancer Center grant (P30-CA196521), the Schneider-Lesser Foundation Award (to J.J.B.-C.) and a Stony Brook-Mount Sinai pilot award (to J.J.B.-C.). C.M. received support from the NIH T32 CA078207 Training Program in Cancer Biology. This work was partially supported by a start-up fund from the Department of Physiology and Biophysics at the University of Illinois at Chicago to A.N. I.T. is the recipient of a Research Grant from the Honors College at the University of Illinois at Chicago and a LASURI award from the College of Liberal Arts and Sciences at the University of Illinois at Chicago. Proteomics services were provided by the UIC Research Resources Center Mass Spectrometry Core, which was established in part by a grant from the Searle Funds at the Chicago Community Trust to the Chicago Biomedical Consortium, and by the Proteomics Core Facility of the Koch Institute for Integrative Cancer Research at MIT, supported in part by a Cancer Center Support Grant from the NCI. Bioinformatic analyses of the proteomics data were performed by the UIC Research Informatics Core, supported in part by the National Center for Advancing Translational Sciences (grant UL1TR002003). J.A.A.-G. and A.R.N. were supported by grants from NIH/NCI (CA109182 and CA196521). J.A.A.-G. is a Samuel Waxman Cancer Research Foundation Investigator. E.J.F. was supported by NCI (P30 CA006973). Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2022",
month = jan,
doi = "10.1038/s43018-021-00291-9",
language = "English",
volume = "3",
pages = "90--107",
journal = "Nature Cancer",
issn = "2662-1347",
publisher = "Nature Research",
number = "1",
}