TY - JOUR
T1 - Pre-osteoblastic MC3T3-E1 cells promote breast cancer growth in bone in a murine xenograft model
AU - Bodenstine, Thomas M.
AU - Beck, Benjamin H.
AU - Cao, Xuemei
AU - Cook, Leah M.
AU - Ismail, Aimen
AU - Kent Powers, J.
AU - Mastro, Andrea M.
AU - Welch, Danny R.
PY - 2011
Y1 - 2011
N2 - The bones are the most common sites of breast cancer metastasis. Upon arrival within the bone microenvironment, breast cancer cells coordinate the activities of stromal cells, resulting in an increase in osteoclast activity and bone matrix degradation. In late stages of bone metastasis, breast cancer cells induce apoptosis in osteoblasts, which further exacerbates bone loss. However, in early stages, breast cancer cells induce osteoblasts to secrete inflammatory cytokines purported to drive tumor progression. To more thoroughly evaluate the role of osteoblasts in early stages of breast cancer metastasis to the bones, we used green fluorescent protein-la beled human breast cancer cell lines MDA-MB-23 1 and MDA-M B-43 5, which both induce osteolysis after intra-fe moral injection in athymic mice, and the murine pre-os teoblastic cell line MC3T3-E 1 to modulate osteoblast populations at the sites of breast cancer metastasis. Breast cancer cells were injected directly into the femur with or without equal numbers of MC3T3-E 1 cells. Tumors grew significantly larger when co-in jected with breast cancer cells and MC3T3-E 1 cells than injected with breast cancer cells alone. Osteolysis was induced in both groups, indicating that MC3T3-E 1 cells did not block the ability of breast cancer cells to cause bone destruction. MC3T3-E 1 cells promoted tumor growth out of the bone into the extraosseous stroma. These data suggest that breast cancer cells and osteoblasts communicate during early stages of bone metastasis and promote tumor growth.
AB - The bones are the most common sites of breast cancer metastasis. Upon arrival within the bone microenvironment, breast cancer cells coordinate the activities of stromal cells, resulting in an increase in osteoclast activity and bone matrix degradation. In late stages of bone metastasis, breast cancer cells induce apoptosis in osteoblasts, which further exacerbates bone loss. However, in early stages, breast cancer cells induce osteoblasts to secrete inflammatory cytokines purported to drive tumor progression. To more thoroughly evaluate the role of osteoblasts in early stages of breast cancer metastasis to the bones, we used green fluorescent protein-la beled human breast cancer cell lines MDA-MB-23 1 and MDA-M B-43 5, which both induce osteolysis after intra-fe moral injection in athymic mice, and the murine pre-os teoblastic cell line MC3T3-E 1 to modulate osteoblast populations at the sites of breast cancer metastasis. Breast cancer cells were injected directly into the femur with or without equal numbers of MC3T3-E 1 cells. Tumors grew significantly larger when co-in jected with breast cancer cells and MC3T3-E 1 cells than injected with breast cancer cells alone. Osteolysis was induced in both groups, indicating that MC3T3-E 1 cells did not block the ability of breast cancer cells to cause bone destruction. MC3T3-E 1 cells promoted tumor growth out of the bone into the extraosseous stroma. These data suggest that breast cancer cells and osteoblasts communicate during early stages of bone metastasis and promote tumor growth.
UR - http://www.scopus.com/inward/record.url?scp=79954492454&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79954492454&partnerID=8YFLogxK
U2 - 10.5732/cjc.010.10582
DO - 10.5732/cjc.010.10582
M3 - Article
C2 - 21352696
AN - SCOPUS:79954492454
SN - 1000-467X
VL - 30
SP - 189
EP - 196
JO - Chinese Journal of Cancer
JF - Chinese Journal of Cancer
IS - 3
ER -