Breast cancer metastasis to bone: a study of the effect of bone cell conditioned media on triple negative breast cancer cells in bone microenvironment
Date
2013
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
University of Delaware
Abstract
Breast cancer is the second leading cause of death in women- behind lung
cancer. Statistics have shown that 1 in 36 women in the United States die from the
pandemic. Triple negative breast cancer, TNBC, which accounts for 10-20% of all
breast cancer subtypes, is classified as aggressive in growth and invasiveness and is
associated with poorer short-term prognosis. Due to their independence from hormone
receptors, these cancer cells lack effective therapeutics and treatment of patients is
limited to chemotherapy. Death occurrence from breast cancer is prevalent in patients
with metastatic breast cancer. In the United States, approximately 200,000 cases of
metastatic breast cancer and 50,000 cases of non-invasive breast cancer are estimated
to be diagnosed annually.
Breast cancer is frequently associated with skeletal metastases. Over 70% of
breast cancer metastasis occurs in bone. Bone metastasis causes bone pain, fracture,
hypercalcemia, and paralysis. This is because tumor-bone interaction in the bone
microenvironment creates a vicious cycle that upsurges bone resorption. While the
effect of triple negative breast cancer tumor cells on bone are widely known, the effect
of bone cells on metastatic triple negative breast cancer cells is not fully understood.
The present study was designed to investigate the effect of bone-conditioned medium on TNBC using conditioned medium from different lineages of cells within the bone
marrow. Conditioned media harvested from new born mice Calvaria, mouse myoblast
cell line C2C12, preosteoblast cell line MC3T3, 8-weeks old mice BMSC, 6-months
old mice BMSC and osteoclast were all used as treatment to determine the effects on
migration of TNBC. Breast cancer cells, MDA-MB-231, extracted from older
Caucasian patients, MDA-MB435, extracted from younger Caucasian patients and
MDA-MB468, extracted from older African American patients were used as triple
negative breast cancer cells. Here, we report that in comparison to the above
conditioned medium, myoblast-conditioned medium greatly inhibited these breast
cancer cells. However, the degree of inhibition depended on the type of TNBC.
Further investigations were conducted to determine the effect of myoblastconditioned
medium on proliferation and invasion activities of TNBC and it was found
that myoblast-conditioned medium greatly inhibited triple negative breast cancer
proliferation and invasion of MDA-MB-435. Additionally, results indicated that
invasion of MDA-MB-231 and MDA-MB-468 to bone was inhibited under the
influence of myoblast-conditioned medium. However, it was observed that minimal
myoblast-conditioned medium inhibited triple negative breast cancer proliferation of
MDA-MB-231 while it promoted triple negative breast cancer proliferation of MDAMB-
468.