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Post-pregnancy Events Promote Breast Cancer Metastasis
Changes
in the tissue environment of the breast that occur after pregnancy promote
the metastasis of breast cancer cells. The
focus on the tumor environment, or stroma, has been gaining strength in
recent years. The human breast undergoes dramatic changes during the
course of pregnancy, lactation, and involution
(the process by which the milk-producing tissue is reabsorbed and the
breast returns to “normal”).
These processes require mammary cells to proliferate, differentiate, and
finally die, events that are partly driven by changes in the environment
surrounding the cells, or extracellular matrix.
How these changes affect the outcome of breast cancer is of great
interest, especially considering
the epidemiological link between breast cancer after pregnancy and poor
prognosis. The
Schedin laboratory at the University of Colorado Health Sciences Center
compared extracellular matrix from mammary glands of rats exhibiting
post-lactation involution to that of virgin rats. The involution matrix
contained higher levels of matrix proteases and degraded proteins and
generally more matrix proteins than virgin matrix, indicating that
involution matrix was undergoing
significant structural changes. In vitro invasion assays established that
human breast tumor cells migrated much better through the involution
matrix than through virgin matrix. They
next performed in vivo experiments to further confirm that post-lactation
involution matrix enhances tumor cell migration (i.e. metastasis). Breast
tumor cells were mixed with either involution or virgin matrix, and the
mixtures were injected into the mammary fat pads of mice. Human tumor
cells formed small mammary tumors, regardless of matrix source; however,
the involution matrix exerted a more powerful push toward metastasis, with
cells spreading to the lung, liver and kidney, expressing
higher levels of the human vascular growth factor VEGF and increasing
blood vessel development. These
data demonstrate the importance of the changing breast environment in the
evolution of breast
cancer. Specifically, changes in the extracellular matrix that occur
during post-pregnancy involution
may actually promote metastasis of breast cancer following pregnancy. These
data may explain why women with breast cancer diagnosed up to 5 years
after pregnancy are at greater risk of developing metastases.
(Adapted
from a Press Release by Audra Cox, www.asip.org/pubs/pr/AJpress.htm). Bibliographical
reference: McDaniel
SM, Rumer KK, Biroc SL, Metz RP, Singh M, Porter W, Schedin P:
“Remodeling of
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