Inhibition of Stem Cell Mobilization in Breast Cancer Patients by a Circulating Factor
Abstract
Some breast cancer patients are candidates for high dose therapy requiring collection of a cytokine-mobilized blood stem cell harvest for subsequent reinfuision to restore hematopoiesis and immune function. A proportion of patients respond poorly to mobilizing cytokines making collection of an adequate harvest inconvenient, prolonged and costly. The hypothesis of this project was that such patients had a circulating inhibitor of stem cell mobilization. Plasma from poorly versus vigorously mobilizing individuals was assayed in a mouse model for its ability to inhibit cytokine mobilization of stem and progenitor cells. There was a significant positive correlation between the number of CD34+ stem cells per collection and inhibition or stimulation of CD45CD34+ cells, GM-CFC and HPP-CFC progenitor cells and spleen weight of mice receiving plasma injections prior to cytokine injection. The majority of individuals who mobilized poorly (less than 106 CD34+ cells/collection) showed inhibition of mobilization. In contrast, plasma from some vigorous mobilizers (over S x 106 CD34+ cells/collection) enhanced mobilization. These data suggest that circulating inhibitor(s) and potentially, stimulator(s) of mobilization are generated as a result of cytokine injection. Genetic factors and prior therapy may influence this response. The inhibitor(s) might be TGF-beta. The identity of the stimulator(s) is unknown. Characterization and manipulation of these factors might permit adequate mobilization of all breast cancer patients.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA381106
Entities
People
- John G. Sharp
Organizations
- University of Nebraska Omaha