DF/HCC Program Affiliation

Angiogenesis, Invasion, and Metastasis
Breast Cancer

Research Abstract

Osteolytic Tumors in Bone: Metastatic breast adenocarcinoma and multiple myeloma cause morbidity and death because of tumor cell interference and "takeover" of the normal regulatory pathways involving bone marrow stromal cells, osteoblasts, and resorptive osteoclasts. We are investigating human breast cancer cells, testing the hypothesis that mimicry of the osteoblast phoneotype provides survival advantages in skeletal metastatic sites. Interaction of breast adnocarcinoma cells with normal bone marrow stromal cells in the metatstatic site stimulates osteoclast dvelopment and bone destruction. We are testing whether the osteolytic reaction to breast adenocarcinoma cells is achieved by upregulation of the osteoclast differentiation receptor, RANK, or its ligand (RANKL), or downregulation of the protective decoy receptor osteoprotegerin (OPG). The identical receptor (RANK) and ligand (RANKL) determine the survival of dendritic cells (antigen-presenting cells) for the continued instruction of T-cells.


Osteolytic Tumors in Bone: Metastatic breast adenocarcinoma and multiple myeloma cause morbidity and death because of tumor cell interference and "takeover" of the normal regulatory pathways involving bone marrow stromal cells, osteoblasts, and resorptive osteoclasts. Interaction of breast adenocarcinoma cells with normal bone marrow stromal cells in the metastatic site stimulates osteoclast development and bone destruction. We are investigating human breast cancer cells, testing two hypotheses: 1) does breast cancer mimicry of the osteoblast phenotype provide survival advantages in skeletal metastatic sites? and 2) is the osteolytic reaction to breast adenocarcinoma cells is achieved by upregulation of the osteoclast differentiation receptor, RANK, or its ligand RANKL, or downregulation of the protective decoy receptor osteoprotegerin OPG? The identical RANK-RANKL receptor-ligand pair determine the survival of dendritic cells (antigen-presenting cells) for the continued instruction of T-cells.

Publications

• MacDonald BT, Joiner DM, Oyserman SM, Sharma P, Goldstein SA, He X, Hauschka PV.Bone mass is inversely proportional to Dkk1 levels in mice.Bone 2007 Sep;41(3):331-9.
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• Danciu TE, Adam RM, Naruse K, Freeman MR, Hauschka PV.Calcium regulates the PI3K-Akt pathway in stretched osteoblasts.FEBS Lett 2003 Feb 11;536(1-3):193-7.
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• Chen L, Adar R, Yang X, Monsonego EO, Li C, Hauschka PV, Yayon A, Deng CX.Gly369Cys mutation in mouse FGFR3 causes achondroplasia by affecting both chondrogenesis and osteogenesis.J Clin Invest 1999 Dec;104(11):1517-25.
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• Asahina I, Sampath TK, Hauschka PV.Human osteogenic protein-1 induces chondroblastic, osteoblastic, and/or adipocytic differentiation of clonal murine target cells.Exp Cell Res 1996 Jan 10;222(1):38-47.
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