Transient Commensal Clonal Interactions Can Drive Tumor Metastasis

To interrogate functional heterogeneity and crosstalk between tumor cells, we generated 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 were eng...

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Veröffentlicht in:bioRxiv
Hauptverfasser: Suha Naffar-Abu Amara, Kuiken, Hendrik J, Selfors, Laura M, Butler, Timothy, Leung, Marco L, Leung, Cheuk T, Kuhn, Elaine P, Kolarova, Teodora R, Hage, Carina, Ganesh, Kripa, Foster, Rosemary, Rueda, Bo R, Aktipis, Athena, Spellman, Paul T, Ince, Tan, Navin, Nicholas, Mills, Gordon B, Bronson, Rodrick T, Brugge, Joan S S
Format: Paper
Sprache:Englisch
Veröffentlicht: Cold Spring Harbor Cold Spring Harbor Laboratory Press 16.01.2020
Cold Spring Harbor Laboratory
Ausgabe:1.1
Schlagworte:
Amphiregulin
Ascites
Cancer Biology
ErbB-2 protein
Metastases
Metastasis
Peritoneum
Transplantation
Tumor cells
Tumors
ISSN:2692-8205, 2692-8205
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Zusammenfassung:To interrogate functional heterogeneity and crosstalk between tumor cells, we generated 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 were 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, grew robustly, generating exclusively malignant ascites. However, multiclonal mixtures formed large solid peritoneal metastases, populated almost entirely by CL31, suggesting that transient cooperative interclonal interactions were sufficient to promote metastasis of CL31. CL31 uniquely harbored ERBB2 amplification, and its acquired metastatic trait was dependent on transient exposure to amphiregulin, which was exclusively secreted by non-tumorigenic clones. Amphiregulin enhanced 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.
Bibliographie:SourceType-Working Papers-1
ObjectType-Working Paper/Pre-Print-1
content type line 50
ISSN:2692-8205
2692-8205
DOI:10.1101/2020.01.16.907071