Systemic endocrine instigation of indolent tumor growth requires osteopontin.
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.
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Sandra S
SS
McAllister
Ann M
AM
Gifford
Ashley L
AL
Greiner
Stephen P
SP
Kelleher
Matthew P
MP
Saelzler
Tan A
TA
Ince
Ferenc
F
Reinhardt
Lyndsay N
LN
Harris
Bonnie L
BL
Hylander
Elizabeth A
EA
Repasky
Robert A
RA
Weinberg
D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D003110:Colonic Neoplasms / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D053495:Osteopontin / Q000378:metabolism*; D014183:Transplantation, Heterologous
D053495:Osteopontin