Systemic endocrine instigation of indolent tumor growth requires osteopontin

作者：McAllister Sandra S; Gifford Ann M; Greiner Ashley L; Kelleher Stephen P; Saelzler Matthew P; Ince Tan A; Reinhardt Ferenc; Harris Lyndsay N; Hylander Bonnie L; Repasky Elizabeth A; Weinberg Robert A^*

来源：Cell, 2008, 133(6): 994-1005.

DOI：10.1016/j.cell.2008.04.045

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.

• 出版日期2008-6-13