Systemic Endocrine Instigation of Indolent Tumor Growth Requires Osteopontin

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

Research output: Contribution to journalArticle

310 Scopus citations

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 languageEnglish (US)
Pages (from-to)994-1005
Number of pages12
JournalCell
Volume133
Issue number6
DOIs
StatePublished - Jun 13 2008
Externally publishedYes

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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    McAllister, S. S., Gifford, A. M., Greiner, A. L., Kelleher, S. P., Saelzler, M. P., Ince, T. A., Reinhardt, F., Harris, L. N., Hylander, B. L., Repasky, E. A., & Weinberg, R. A. (2008). Systemic Endocrine Instigation of Indolent Tumor Growth Requires Osteopontin. Cell, 133(6), 994-1005. https://doi.org/10.1016/j.cell.2008.04.045