The research of this project is focused on a newly discovered mechanism that operates as an important determinant of the growth of tumors. Carcinomas in general, and breast cancers in particular, are known to depend on recruited mesenchymal cells that form the tumor-associated stroma and provide vital physiologic support to the epithelial cancer cells. These mesenchymal cells derive from normal host tissue adjacent to the growing tumor as well as from progenitor cells that originate in the bone marrow. However, the mechanisms that allow the recruitment of such bone marrow progenitors and the importance of their role in overall tumor growth remain poorly understood. The research described here indicates that the slow growth of indolent tumors can be attributed in some cases, and perhaps in many, to the inability of the cancer cells to effectively recruit stromal progenitors from the marrow. This defect, in turn, can be ascribed to the fact that these indolent tumor cells are unable to release endocrine signals that perturb the bone marrow, causing it to activate and mobilize into the circulation stromal precursor cells that may subsequently be recruited by the tumor cells. Without this bone marrow-activating power, these indolent tumor cells fail to effectively recruit stromal precursors from the circulation and remain either dormant or slowly growing. In contrast, some vigorously growing tumors are endowed with the endocrine signaling ability, which we term
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