Do osteosarcoma cells stay diverse after metastasis?
Across ~48k cells, osteosarcoma tumors kept distinct transcriptional subsets while adapting to bone and lung niches—even under clonal selection.
Source
Osteosarcoma tumors maintain intra-tumoral transcriptional heterogeneity during bone and lung colonization
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Do osteosarcoma cells stay diverse after metastasis?
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47,977 cells profiled.
We investigated single-cell RNA-sequencing profiles of 47,977 cells obtained from cell line and patient-derived xenograft models
Tumor cells maintained phenotypic heterogeneity during bone/lung colonization.
Tumor cells maintained phenotypic heterogeneity as they responded to the selective pressures imposed during bone and lung colonization
What they did
Profiled cell-line and PDX models with single-cell RNA-seq as tumors colonized tibia and lung, and combined lineage tracing with transcriptomics.
What they found
Heterogeneous transcriptional subsets persisted; a glucose-metabolism feature validated by immunofluorescence; lung colonization enriched multiple clones whose profiles stayed across generations.
The limits
What it doesn't show
Does not prove a single clinical therapy target or map early dissemination steps outside colonization bottlenecks.
Key terms
- Intra-tumoral heterogeneity
- Coexistence of transcriptionally distinct malignant cell states in one tumor.
- scRNA-seq
- Single-cell RNA sequencing used to profile cell states.
- PDX
- Patient-derived xenograft grown in mice.
- Lung colonization
- Establishment of metastatic growth after cells reach the lung.
- Lineage tracing
- Labeling clones to track which lineages expand.
- Clonal selection
- Preferential expansion of fitter clones under stress.
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Approximate cells profiled:
Common questions
How many cells?
47,977.
Model systems?
Cell lines and PDX orthotopic bone + lung mets.
Key validated feature?
Glucose-metabolism heterogeneity (immunofluorescence).
Main conclusion?
Heterogeneity persists even with clonal selection.
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