Effects of Growth Factors on Proliferation and Differentiation of Human Mammary Stem/Progenitor Cells
Loading...
Authors
Foley, Jessica M.
Issue Date
2003
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Stem/progenitor cells (SPC) are the multi-potent progenitors that give rise to all
mammary gland lineages. With cancer biology beginning to focus on tumorigenic stem
cells as being the origin of clinically relevant metastatic cells, isolation of normal
mammary SPCs would prove essential for comparison studies between the healthy and
tumorigenic cell populations. However, the isolation and purification of SPCs has
remained difficult, as no assay has been developed which demonstrates the two key stem cell properties: ability to differentiate into multi-lineage progeny and to self-renew. In an effort to cultivate a suspension culture enriched in SPCs an assay was developed in which human mammary epithelial cells (HMEC) were grown in low-adherence conditions in the form of mammospheres. These mammospheres were found to generate more multilineage colonies when placed in differentiating conditions, signaling the presence of SPCs. Additionally, this culture system was used to investigate the effects of various growth factors implicated in mammary gland morphogenesis on cell fate determination.
We showed that LIF, SCF, EGF, and bFGF support proliferation of HMEC in an
undifferentiated state in suspension culture, whereas PE and BMP4 favor differentiation
along ductal epithelial and myoepithelial lineages respectively. Direct study of SPCs
would not only be useful in studying mammary gland development, but also provide a
means of comparison, through analysis of gene and surface protein expression, between healthy and tumorigenic tissues. This comparison could facilitate the identification of specific pathways important for growth and survival of tumors and permit the development of new therapeutic strategies targeting these pathways.
Description
vi, 57 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.