Biomedical Engineering Reference
In-Depth Information
5 Central Importance of the Stroma
Luminal epithelial cells interact with a surrounding microenvironment (Stern-
licht, 2006). In part, these interactions direct normal mammary gland develop-
ment. Altering luminal epithelial cell interaction with the extracellular matrix
and local microenvironment might induce abnormal intracellular signaling
pathways that affect the development and progression of breast tumors
(Gupta andMassague, 2006). Mina Bissell and her group at Lawrence Berkeley
Laboratory have been studying these kinds of interactions for the past 20+
years (for review see LaBarge et al., 2007). A central signal pathway for
mammary gland development and breast cancer progression involves the
expression of estrogen receptors (Novaro et al., 2004). In a study using cultured
nonmalignant mammary epithelial cells, the basement membrane molecules,
laminin-1 and collagen-IV, were found to be involved in maintenance of estro-
gen receptor alpha expression (Novaro et al., 2003). Other workers found that
this response could be interfered through the disruption of cell-extracellular
matrix adhesion. Phenotypically normal mammary epithelial cells have been
used to dissect the promoter region of the ER alpha receptor involved in response
to the basement membrane. Amalignant cell line sharing a common lineage with
normal mammary cells provide the insight that overexpression of ER alpha
accompanied unresponsiveness to normal basement membrane regulation
found in those malignant cells. One interpretation of these data is that cross-
talk between different signaling pathways is a requirement in the constitution or
proper functional tissue organization and when this cell-cell interaction goes
awry, the malignant phenotype may result.
Normal tissue homeostasis is maintained by dynamic interactions between
epithelial cells and their microenvironment. As tissue becomes cancerous, there
are reciprocal interactions between neoplastic cells, adjacent normal cells such
as stroma and endothelium, and their microenvironments. The current domi-
nant paradigm wherein multiple genetic lesions provide both the impetus for,
and the Achilles heel of, cancer might be inadequate to understand cancer as a
disease process.
6 Breast Cancer Stem Cells
AUniversity of Michigan group recently identified a small population of cancer
stem cells in breast tumors that has changed the way many scientists view cancer
(Al-Hajj et al., 2003; Hemmati et al., 2003). These cancer stem cells represent
only 1% of the tumor and were the only cells in the tumor capable of trans-
planting the tumor into nude mice. This suggests that the terms cancer stem cells
and tumor-initiating cells are functionally synonymous. Additional studies
have presented data that long-established cell lines, even HeLa cells, contain a
minor population of cells with some of the same tumor-initiating properties as
