Table 2.
Summary of experiments comparing the metastatic potential of single and clustered tumor cells.
| Citation | Model | Method | Findings |
|---|---|---|---|
| (Watanabe, 1954) | Mouse bronchogenic carcinoma | Jugular injection into mice | 92% take rate for clusters, 0% for single cells |
| (Fidler, 1973) | B16 mouse melanoma | Tail vein injection into mice | ~3-fold more lung metastases formed in cluster-injected mice after 2 weeks |
| (Liotta et al., 1976) | T-241 fibrosarcoma | Tail vein injection into mice | 13 to 25-fold more lung metastases formed in cluster-injected mice after 12 days |
| (Aceto et al., 2014) | MDA-MB-231-LM2 human breast cancer cell line | Orthotopic transplant into mice | ~50-fold more lung metastases formed by CTC clusters from tumor transplants relative to single CTCs |
| 4T1 mouse breast cancer cell line | Orthotopic transplant into mice | ~23-fold more lung metastases formed by CTC clusters from tumor transplants relative to single CTCs | |
| (Maddipati and Stanger, 2015) | KCPX mouse model of pancreatic cancer | Intraperitoneal injection into mice | >2-fold more metastases formed in cluster-injected mice after 3 weeks |
| KCPX mouse model of pancreatic cancer | Retro-orbital injection into mice | >15-fold more lung metastases formed in cluster-injected mice after 3 weeks | |
| KCPX mouse model of pancreatic cancer | Multi-color spontaneous mouse tumor model | 80% of large metastatic lesions to peritoneum and diaphragm arose from multiple cells | |
| (Cheung et al., 2016) | MMTV-PyMT mouse model of Luminal B breast cancer | Orthotopic transplant into mice | Estimated >97% of lung metastases were derived from clusters (95% CI: 74–100%) |
| MMTV-PyMT mouse model of Luminal B breast cancer | Tail vein injection into mice | >100-fold more lung metastases formed by cluster-injected mice after 3 weeks | |
| (Zajac et al., 2018) | Colorectal cancer PDX | Intraperitoneal injection | >20-fold higher tumor burden in cluster-injected mice after 40 days |
| (Allen et al., 2019) | B16F10 mouse melanoma cell line | Tail vein injection into mice | ~2-fold higher BLI signal of cluster-injected mice after 10 days |
| A375 human melanoma cell line | Tail vein injection into mice | ~3-fold higher BLI signal of cluster-injected mice after 10 days | |
| (Liu et al., 2019) | Breast cancer PDX | Orthotopic transplant into mice | 54% of lung metastases were polyclonal 6–8 weeks after transplant (based on 2-color fluorescence) |
| Breast cancer PDX | Tail vein injection into mice | >5-fold higher BLI signal of cluster-injected mice after 8 weeks | |
| (Lo et al., 2020) | 4T1 mouse breast cancer cell line | Tail vein injection into mice | ~8-fold higher BLI signal of cluster-injected Balb/c mice after 7 days vs. single cells |
| AT3 mouse breast cancer cell line | Tail vein injection into mice | ~500-fold higher BLI signal of cluster-injected C57BL/6 mice after 25 days vs. single cells | |
| (Wrenn et al., 2020) | MMTV-PyMT mouse model of Luminal B breast cancer | Tail vein injection into mice | 141 to 532-fold more lung metastases formed in cluster-injected mice after 3 weeks |
| (Wrenn et al., 2020) | MMTV-PyMT mouse model of Luminal B breast cancer | Intracardiac injection into mice | 7.6-fold more metastases to systemic organs in cluster injected mice after 6 weeks |
Summary of studies assessing the metastatic potential of single or clustered tumor cells in various mouse models of cancer.