Julie Ann Sterling, Ph.D.
Assistant Professor of Medicine (Clinical Pharmacology )
Assistant Professor of Cancer Biology
Cancer metastasis to bone and tumor-induced bone disease.
Our research focuses on tumors that metastasize to bone and the subsequent changes in bone that occur. While our research focuses primarily on breast cancer metastasis to bone, we also study lung, prostate, and myeloma which are tumors that can reside in bone and induce bone disease. Once breast tumors establish in bone they can stimulate bone destructions, which leads to increased fracture rates and pain in patients. Importantly, there are no cures for tumors once they have established in bone. We study the mechanisms that regulate metasis to bone and induce bone destruction, which requires molecular biology, engineering, animal models, and small animal imaging. These techniques together have helped us better understand tumor-induced bone disease and have allowed us to begin testing promising therapeutics in small animal models of tumor-induced bone disease.
Specifically, we have determined that the developmental transcription factor Gli2 is upreguated when tumor cells metastasize to bone and that this leads to the production of the the osteolytic (bone destructive) factor parathyroid hormone related protein (PTHrP). While it is still unclear why Gli2 is expressed in some tumor cells, our work has demonstrated that the physical stiffness of bone stimulates Gli2 and PTHrP expression through a combination of transforming growth factor-beta and mechanotransduction signaling. Currently we are testing the applicability of inhibitors to these pathways to determine their efficacy in our pre-clinical models of cancer metastasis to bone.
- Li, X, Sterling, JA, Fan, KH, Vessella, RL, Shyr, Y, Hayward, SW, Matrisian, LM, Bhowmick, NA Loss of TGF-¿¿ responsiveness in prostate stromal cells alters chemokine levels and facilitates the development of mixed osteoblastic/osteolytic bone lesions. Mol Cancer Res, 10(4), 494-503, 2012.
- Campbell, JP, Merkel, AR, Masood-Campbell, SK, Elefteriou, F, Sterling, JA Models of bone metastasis. J Vis Exp, (67), e4260, 2012.
- Danilin, S, Merkel, AR, Johnson, JR, Johnson, RW, Edwards, JR, Sterling, JA Myeloid-derived suppressor cells expand during breast cancer progression and promote tumor-induced bone destruction. Oncoimmunology, 1(9), 1484-1494, 2012.
- Campbell, JP, Karolak, MR, Ma, Y, Perrien, DS, Masood-Campbell, SK, Penner, NL, Munoz, SA, Zijlstra, A, Yang, X, Sterling, JA, Elefteriou, F Stimulation of host bone marrow stromal cells by sympathetic nerves promotes breast cancer bone metastasis in mice. PLoS Biol, 10(7), e1001363, 2012.
- Sterling, JA, Edwards, JR, Martin, TJ, Mundy, GR Advances in the biology of bone metastasis: how the skeleton affects tumor behavior. Bone, 48(1), 6-15, 2011.
- Sterling, JA, Guelcher, SA Bone Structural Components Regulating Sites of Tumor Metastasis. Curr Osteoporos Rep, 2011.
- Guelcher, SA, Sterling, JA Contribution of bone tissue modulus to breast cancer metastasis to bone. Cancer Microenviron, 4(3), 247-59, 2011.
- Johnson, LC, Johnson, RW, Munoz, SA, Mundy, GR, Peterson, TE, Sterling, JA Longitudinal live animal micro-CT allows for quantitative analysis of tumor-induced bone destruction. Bone, 48(1), 141-51, 2011.
- Johnson, RW, Nguyen, MP, Padalecki, SS, Grubbs, BG, Merkel, AR, Oyajobi, BO, Matrisian, LM, Mundy, GR, Sterling, JA TGF-beta promotion of Gli2-induced expression of parathyroid hormone-related protein, an important osteolytic factor in bone metastasis, is independent of canonical Hedgehog signaling. Cancer Res, 71(3), 822-31, 2011.
- Ruppender, NS, Merkel, AR, Martin, TJ, Mundy, GR, Sterling, JA, Guelcher, SA Matrix rigidity induces osteolytic gene expression of metastatic breast cancer cells. PLoS One, 5(11), e15451, 2010.
- Sterling, JA, Wu, L, Banerji, SS PARP regulates TGF-beta receptor type II expression in estrogen receptor-positive breast cancer cell lines. Anticancer Res, 26(3A), 1893-901, 2006.
- Sterling, JA, Oyajobi, BO, Grubbs, B, Padalecki, SS, Munoz, SA, Gupta, A, Story, B, Zhao, M, Mundy, GR The hedgehog signaling molecule Gli2 induces parathyroid hormone-related peptide expression and osteolysis in metastatic human breast cancer cells. Cancer Res, 66(15), 7548-53, 2006.