Abstract
The limitations of cancer cell lines have led to the development of direct patient-derived xenograft models. However, the interplay between the implanted human cancer cells and recruited mouse stromal and immune cells alters the tumor microenvironment and limits the value of these models. To overcome these constraints, we have developed a technique to expand human hematopoietic stem and progenitor cells (HSPCs) and use them to reconstitute the radiation-depleted bone marrow of a NOD/SCID/IL2rg-/-(NSG) mouse on which a patient's tumor is then transplanted (XactMice). The human HSPCs produce immune cells that home into the tumor and help replicate its natural microenvironment. Despite previous passage on nude mice, the expression of epithelial, stromal and immune genes in XactMice tumors aligns more closely to that of the patient tumor than to those grown in non-humanized mice-an effect partially facilitated by human cytokines expressed by both the HSPC progeny and the tumor cells. The human immune and stromal cells produced in the XactMice can help recapitulate the microenvironment of an implanted xenograft, reverse the initial genetic drift seen after passage on non-humanized mice and provide a more accurate tumor model to guide patient treatment.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 290-300 |
| Number of pages | 11 |
| Journal | Oncogene |
| Volume | 35 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jan 21 2016 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics
Cite this
XactMice : Humanizing mouse bone marrow enables microenvironment reconstitution in a patient-derived xenograft model of head and neck cancer. / Morton, J. J.; Bird, G.; Keysar, S. B.; Astling, D. P.; Lyons, T. R.; Anderson, R. T.; Glogowska, M. J.; Estes, P.; Eagles, J. R.; Le, P. N.; Gan, G.; McGettigan, B.; Fernandez, P.; Padilla-Just, N.; Varella-Garcia, M.; Song, J. I.; Bowles, D. W.; Schedin, Pepper; Tan, A. C.; Roop, D. R.; Wang, X. J.; Refaeli, Y.; Jimeno, A.
In: Oncogene, Vol. 35, No. 3, 21.01.2016, p. 290-300.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - XactMice
T2 - Humanizing mouse bone marrow enables microenvironment reconstitution in a patient-derived xenograft model of head and neck cancer
AU - Morton, J. J.
AU - Bird, G.
AU - Keysar, S. B.
AU - Astling, D. P.
AU - Lyons, T. R.
AU - Anderson, R. T.
AU - Glogowska, M. J.
AU - Estes, P.
AU - Eagles, J. R.
AU - Le, P. N.
AU - Gan, G.
AU - McGettigan, B.
AU - Fernandez, P.
AU - Padilla-Just, N.
AU - Varella-Garcia, M.
AU - Song, J. I.
AU - Bowles, D. W.
AU - Schedin, Pepper
AU - Tan, A. C.
AU - Roop, D. R.
AU - Wang, X. J.
AU - Refaeli, Y.
AU - Jimeno, A.
PY - 2016/1/21
Y1 - 2016/1/21
N2 - The limitations of cancer cell lines have led to the development of direct patient-derived xenograft models. However, the interplay between the implanted human cancer cells and recruited mouse stromal and immune cells alters the tumor microenvironment and limits the value of these models. To overcome these constraints, we have developed a technique to expand human hematopoietic stem and progenitor cells (HSPCs) and use them to reconstitute the radiation-depleted bone marrow of a NOD/SCID/IL2rg-/-(NSG) mouse on which a patient's tumor is then transplanted (XactMice). The human HSPCs produce immune cells that home into the tumor and help replicate its natural microenvironment. Despite previous passage on nude mice, the expression of epithelial, stromal and immune genes in XactMice tumors aligns more closely to that of the patient tumor than to those grown in non-humanized mice-an effect partially facilitated by human cytokines expressed by both the HSPC progeny and the tumor cells. The human immune and stromal cells produced in the XactMice can help recapitulate the microenvironment of an implanted xenograft, reverse the initial genetic drift seen after passage on non-humanized mice and provide a more accurate tumor model to guide patient treatment.
AB - The limitations of cancer cell lines have led to the development of direct patient-derived xenograft models. However, the interplay between the implanted human cancer cells and recruited mouse stromal and immune cells alters the tumor microenvironment and limits the value of these models. To overcome these constraints, we have developed a technique to expand human hematopoietic stem and progenitor cells (HSPCs) and use them to reconstitute the radiation-depleted bone marrow of a NOD/SCID/IL2rg-/-(NSG) mouse on which a patient's tumor is then transplanted (XactMice). The human HSPCs produce immune cells that home into the tumor and help replicate its natural microenvironment. Despite previous passage on nude mice, the expression of epithelial, stromal and immune genes in XactMice tumors aligns more closely to that of the patient tumor than to those grown in non-humanized mice-an effect partially facilitated by human cytokines expressed by both the HSPC progeny and the tumor cells. The human immune and stromal cells produced in the XactMice can help recapitulate the microenvironment of an implanted xenograft, reverse the initial genetic drift seen after passage on non-humanized mice and provide a more accurate tumor model to guide patient treatment.
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UR - http://www.scopus.com/inward/citedby.url?scp=84955377769&partnerID=8YFLogxK
U2 - 10.1038/onc.2015.94
DO - 10.1038/onc.2015.94
M3 - Article
C2 - 25893296
AN - SCOPUS:84955377769
VL - 35
SP - 290
EP - 300
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 3
ER -