Transient commensal clonal interactions can drive tumor metastasis

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 intraperitonea...

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Vydané v:Nature communications Ročník 11; číslo 1; s. 5799 - 17
Hlavní autori: Naffar-Abu Amara, Suha, Kuiken, Hendrik J., Selfors, Laura M., Butler, Timothy, Leung, Marco L., Leung, Cheuk T., Kuhn, Elaine P., Kolarova, Teodora, Hage, Carina, Ganesh, Kripa, Panayiotou, Richard, Foster, Rosemary, Rueda, Bo R., Aktipis, Athena, Spellman, Paul, Ince, Tan A., Xiu, Joanne, Oberley, Matthew, Gatalica, Zoran, Navin, Nicholas, Mills, Gordon B., Bronson, Rodrick T., Brugge, Joan S.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: London Nature Publishing Group UK 16.11.2020
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Amphiregulin
Ascites
Crosstalk
Deoxyribonucleic acid
DNA
ErbB-2 protein
Gastric cancer
Gene sequencing
Heterogeneity
Humanities and Social Sciences
Metastases
Metastasis
multidisciplinary
Ovarian cancer
Ovarian carcinoma
Ovaries
Peritoneum
Populations
Science
Science (multidisciplinary)
Subpopulations
Transplantation
Tumor cells
Tumors
ISSN:2041-1723, 2041-1723
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Shrnutí: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. Cooperative interactions among tumor cells may have important implications for metastasis. Here, the authors examined the spatio-temporal nature of interactions among clonal populations of ovarian carcinoma cells and found that transient interactions cells can promote metastases via commensal interactions.
Bibliografia:ObjectType-Article-1
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-020-19584-1