Table 1.
Identification of human primary tumor CSC biomarkers using in vivo assays
Cancer | Animal | Type of injection | Treatment of recipient mice | Injection with Matrigel | Percentage of CSC-enriched population in tumor | Biomarkers | Minimal number of biomarker + cells to obtain a tumor | Reference |
ALL (B-ALL) | NOD/SCID/IL2rγc−/− newborns | Intravenous | Sublethal irradiation | No | 82.50% | CD34+/CD19+ | 2–6 × 104 | Kong et al., 2008 |
AML | NOD/SCID | Intravenous | Sublethal irradiation | No | 0.75% | CD34+/CD38− | 2 × 105 | Bonnet and Dick, 1997 |
AML | NOD/SCID, NOD/SCID/β2m−/− and NOD/SCID/IL2rγc−/− | Intravenous and intrabone | IVIG of CD122 pretreatment and sublethal irradiation | No | 0.076% (*) | CD34+/CD38− (*) or CD34+/CD38+ (**) (in samples with lowest CD34+/CD38− fraction) | 7.5 × 103 (*) or 106 (**) | Taussig et al., 2008 |
AML | NOD/SCID | Intrafemoral | IVIG of CD122 pretreatment and sublethal irradiation | No | 0.06–0.00009% of bulk | NA | NA | Eppert et al., 2011 |
Bladder | Rag2γcDKO | Intradermal | NA | Yes | 3–36.3% | CD44 | 100 | Chan et al., 2009 |
Breast | NOD/SCID | Mammary fat pad | VP-16, estrogen pellets | No | 11–35% | ESA+/CD44high/CD24low-neg | 200 | Al Hajj et al., 2003 |
Breast | NOD/SCID | Humanized mammary fat pad | Estrogen pellets | Yes | 3–10% | ALDH-1+ | 500 | Ginestier et al., 2007 |
Brain | NOD/SCID | Intracranial | NA | No | 6–29% | CD133+ | 100 | Singh et al., 2004 |
Colorectal | NOD/SCID | Renal capsule | Sublethal irradiation | Yes | 1.8–24.5% | CD133+ | 100 | O’Brien et al., 2007 |
Colorectal | NOD/SCID | Subcutaneous | NA | No | 2.60% | ESAhigh/CD44+ | 200 | Dalerba et al., 2007 |
Colorectal | NOD/SCID | Subcutaneous | NA | Yes | 3.50% | ALDH-1+ | 25 serially passaged | Huang et al., 2009 |
Head and neck squamous cell carcinoma | NOD/SCID and Rag2γcDKO | Subcutaneous | NA | Yes | 10–12% | CD44+ | 5000 | Prince et al., 2007 |
Liver | SCID | Intrahepatic | NA | No | 2.50% | CD45−/CD90+ | 103 | Yang et al., 2008 |
Lung | SCID and NUDE | Subcutaneous, after in vitro expansion | NA | Yes | 0.4–1.5% | CD133+ | 104 | Eramo et al., 2008 |
Lung | NOD/SCID/IL2rγc−/− | Subcutaneous | NA | Yes | Median 15% | lin-/CD166+ | ≤500 | Zhang et al., 2012 |
Melanoma | NOD/SCID | Subcutaneous | NA | No | 1.6-20.4% | ABCB5+ | 105 | Schatton et al., 2008 |
Melanoma | Rag2γcDKO | Intradermal | NA | Yes | 2.5–41% | CD271+ | 100 | Boiko et al., 2010 |
Melanoma | NOD/SCID/IL2rγc−/− | Subcutaneous | NA | Yes | NA | NA | 1 (in 28% of cases) | Quintana et al., 2010 |
Melanoma | NUDE, (NOD/SCID, NOD/SCID/IL2rγc−/−) | Subcutaneous | NA | Yes | 8–11% | CD271+ | 1000 | Civenni et al., 2011 |
Pancreatic | NOD/SCID | Subcutaneous and intrapancreatic | NA | Yes | 0.2-0.8% | ESA+/CD44+/CD24+ | 100 | Li et al., 2007 |
Pancreatic | NUDE | Intrapancreatic | NA | No | 3.6 cells per high-power field | ESA+/CD133+ | 500 | Hermann et al., 2007 |
Studies reporting the existence of enriched human CSC populations are listed. In the first five columns, the main parameters influencing the efficiency of tumor engraftment are listed. From left to right: the tumor entity, the type of immunocompromised mouse strain used, the route of transplantation of human tumor cells, preconditioning of the recipient mice, treatment of mice during the assay, and whether the tumor cells were mixed with Matrigel upon transplantation. In the next four columns, the main results of these studies are summarized. From left to right: the frequency of the identified CSC-enriched population observed in the given tumor entity, the biomarkers identified for this CSC-enriched population, and the minimal number of tumor cells expressing these biomarkers able to give rise to a human tumor as well as the reference of the corresponding study. *, results for the CD34+/CD38− population. **, results for the CD34+/CD38+ population.