Transient commensal clonal interactions can drive tumor metastasis.

Autor: Naffar-Abu Amara S; Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA., Kuiken HJ; Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA., Selfors LM; Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA., Butler T; Department of Molecular and Medical Genetics, Oregon Health & Science University Portland, Portland, OR, 97239-3098, USA.; Cancer, Ageing and Somatic Mutation, Wellcome Trust Sanger Institute, Hinxton, UK., Leung ML; Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.; The Center for Applied Genomics, Children's Hospital of Philadelphia, Pennsylvania, PA, 19104, USA., Leung CT; Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA.; Department of Pharmacology, Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN, 55455, USA., Kuhn EP; Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA.; Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, 03766, USA., Kolarova T; Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA.; Department of Obstetrics & Gynecology, University of Washington, Seattle, WA, 98195, USA., Hage C; Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA.; Roche Innovation Center Munich, Roche Pharmaceutical Research and Early Development, Nonnenwald 2, 82377, Penzberg, Germany., Ganesh K; Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA.; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.; The Biochemistry, Structural, Developmental, Cell and Molecular Biology Allied PhD Program, Weill Cornell Medicine, New York, NY, 10065, USA., Panayiotou R; Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA., Foster R; Vincent Center for Reproductive Biology and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, 02114, USA.; Harvard Medical School, Boston, MA, 02115, USA., Rueda BR; Vincent Center for Reproductive Biology and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, 02114, USA.; Harvard Medical School, Boston, MA, 02115, USA., Aktipis A; Arizona Cancer Evolution Center and Department of Psychology, Arizona State University, Tempe, AZ, 85281, USA., Spellman P; Department of Molecular and Medical Genetics, Oregon Health & Science University Portland, Portland, OR, 97239-3098, USA., Ince TA; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.; New York Presbyterian-Brooklyn Methodist Hospital, Brooklyn, NY, 11215, USA., Xiu J; Caris Life Sciences, Phoenix, AZ, 85040, USA., Oberley M; Caris Life Sciences, Phoenix, AZ, 85040, USA., Gatalica Z; Caris Life Sciences, Phoenix, AZ, 85040, USA.; Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA., Navin N; Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Mills GB; Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University Knight Cancer Institute, Portland, OR, 97239-3098, USA., Bronson RT; Rodent Histopathology Core, Harvard Medical School, Boston, MA, 02115, USA., Brugge JS; Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA. joan_brugge@hms.harvard.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2020 Nov 16; Vol. 11 (1), pp. 5799. Date of Electronic Publication: 2020 Nov 16.
DOI: 10.1038/s41467-020-19584-1
Abstrakt: The extent and importance of functional heterogeneity and crosstalk between tumor cells is poorly understood. Here, we describe the generation of clonal populations from a patient-derived ovarian clear cell carcinoma model which forms malignant ascites and solid peritoneal tumors upon intraperitoneal transplantation in mice. The clonal populations are engineered with secreted Gaussia luciferase to monitor tumor growth dynamics and tagged with a unique DNA barcode to track their fate in multiclonal mixtures during tumor progression. Only one clone, CL31, grows robustly, generating exclusively malignant ascites. However, multiclonal mixtures form large solid peritoneal metastases, populated almost entirely by CL31, suggesting that transient cooperative interclonal interactions are sufficient to promote metastasis of CL31. CL31 uniquely harbors ERBB2 amplification, and its acquired metastatic activity in clonal mixtures is dependent on transient exposure to amphiregulin, which is exclusively secreted by non-tumorigenic clones. Amphiregulin enhances CL31 mesothelial clearance, a prerequisite for metastasis. These findings demonstrate that transient, ostensibly innocuous tumor subpopulations can promote metastases via "hit-and-run" commensal interactions.
Databáze: MEDLINE