Abstract
The effects of primary tumors on the host systemic environment and resulting contributions of the host to tumor growth are poorly understood. Here, we find that human breast carcinomas instigate the growth of otherwise-indolent tumor cells, micrometastases, and human tumor surgical specimens located at distant anatomical sites. This systemic instigation is accompanied by incorporation of bone-marrow cells (BMCs) into the stroma of the distant, once-indolent tumors. We find that BMCs of hosts bearing instigating tumors are functionally activated prior to their mobilization; hence, when coinjected with indolent cells, these activated BMCs mimic the systemic effects imparted by instigating tumors. Secretion of osteopontin by instigating tumors is necessary for BMC activation and the subsequent outgrowth of the distant otherwise-indolent tumors. These results reveal that outgrowth of indolent tumors can be governed on a systemic level by endocrine factors released by certain instigating tumors, and hold important experimental and therapeutic implications.
| Original language | English |
|---|---|
| Pages (from-to) | 994-1005 |
| Number of pages | 12 |
| Journal | Cell |
| Volume | 133 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 13 2008 |
| Externally published | Yes |
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Keywords
- CELLCYCLE
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
Cite this
Systemic Endocrine Instigation of Indolent Tumor Growth Requires Osteopontin. / McAllister, Sandra S.; Gifford, Ann M.; Greiner, Ashley L.; Kelleher, Stephen P.; Saelzler, Matthew P.; Ince, Tan; Reinhardt, Ferenc; Harris, Lyndsay N.; Hylander, Bonnie L.; Repasky, Elizabeth A.; Weinberg, Robert A.
In: Cell, Vol. 133, No. 6, 13.06.2008, p. 994-1005.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Systemic Endocrine Instigation of Indolent Tumor Growth Requires Osteopontin
AU - McAllister, Sandra S.
AU - Gifford, Ann M.
AU - Greiner, Ashley L.
AU - Kelleher, Stephen P.
AU - Saelzler, Matthew P.
AU - Ince, Tan
AU - Reinhardt, Ferenc
AU - Harris, Lyndsay N.
AU - Hylander, Bonnie L.
AU - Repasky, Elizabeth A.
AU - Weinberg, Robert A.
PY - 2008/6/13
Y1 - 2008/6/13
N2 - The effects of primary tumors on the host systemic environment and resulting contributions of the host to tumor growth are poorly understood. Here, we find that human breast carcinomas instigate the growth of otherwise-indolent tumor cells, micrometastases, and human tumor surgical specimens located at distant anatomical sites. This systemic instigation is accompanied by incorporation of bone-marrow cells (BMCs) into the stroma of the distant, once-indolent tumors. We find that BMCs of hosts bearing instigating tumors are functionally activated prior to their mobilization; hence, when coinjected with indolent cells, these activated BMCs mimic the systemic effects imparted by instigating tumors. Secretion of osteopontin by instigating tumors is necessary for BMC activation and the subsequent outgrowth of the distant otherwise-indolent tumors. These results reveal that outgrowth of indolent tumors can be governed on a systemic level by endocrine factors released by certain instigating tumors, and hold important experimental and therapeutic implications.
AB - The effects of primary tumors on the host systemic environment and resulting contributions of the host to tumor growth are poorly understood. Here, we find that human breast carcinomas instigate the growth of otherwise-indolent tumor cells, micrometastases, and human tumor surgical specimens located at distant anatomical sites. This systemic instigation is accompanied by incorporation of bone-marrow cells (BMCs) into the stroma of the distant, once-indolent tumors. We find that BMCs of hosts bearing instigating tumors are functionally activated prior to their mobilization; hence, when coinjected with indolent cells, these activated BMCs mimic the systemic effects imparted by instigating tumors. Secretion of osteopontin by instigating tumors is necessary for BMC activation and the subsequent outgrowth of the distant otherwise-indolent tumors. These results reveal that outgrowth of indolent tumors can be governed on a systemic level by endocrine factors released by certain instigating tumors, and hold important experimental and therapeutic implications.
KW - CELLCYCLE
UR - http://www.scopus.com/inward/record.url?scp=44649088833&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=44649088833&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2008.04.045
DO - 10.1016/j.cell.2008.04.045
M3 - Article
C2 - 18555776
AN - SCOPUS:44649088833
VL - 133
SP - 994
EP - 1005
JO - Cell
JF - Cell
SN - 0092-8674
IS - 6
ER -