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Vanderbilt-Ingram Cancer CenterVanderbilt-Ingram Cancer Center

 
Julie Ann  Sterling

Julie Ann Sterling, Ph.D.

Assistant Professor of Medicine (Clinical Pharmacology )
Assistant Professor of Cancer Biology
Researcher

Contact Information:

615-322-4364

Research Description

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.

Publications
  • 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. 2012 Dec 12/1/2012; 1(9): 1484-94. PMID: 23264895, PMCID: PMC3525604, PII: 2012ONCOIMM0181, DOI: 10.4161/onci.21990, ISSN: 2162-4011.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23264895.
  • 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 [print-electronic]. 2012 Jul; 10(7): e1001363. PMID: 22815651, PMCID: PMC3398959, PII: PBIOLOGY-D-12-00249, DOI: 10.1371/journal.pbio.1001363, ISSN: 1545-7885.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/22815651.
  • Li X, Sterling JA, Fan KH, Vessella RL, Shyr Y, Hayward SW, Matrisian LM, Bhowmick NA. Loss of TGF-ß responsiveness in prostate stromal cells alters chemokine levels and facilitates the development of mixed osteoblastic/osteolytic bone lesions. Mol. Cancer Res [print-electronic]. 2012 Apr; 10(4): 494-503. PMID: 22290877, PMCID: PMC3900026, PII: 1541-7786.MCR-11-0506, DOI: 10.1158/1541-7786.MCR-11-0506, ISSN: 1557-3125.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/22290877.
  • Campbell JP, Merkel AR, Masood-Campbell SK, Elefteriou F, Sterling JA. Models of bone metastasis. J Vis Exp. 2012; (67): e4260. PMID: 22972196, PMCID: PMC3490264, PII: 4260, DOI: 10.3791/4260, ISSN: 1940-087X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/22972196.
  • Guelcher SA, Sterling JA. Contribution of bone tissue modulus to breast cancer metastasis to bone. Cancer Microenviron [print-electronic]. 2011 Dec; 4(3): 247-59. PMID: 21789687, PMCID: PMC3234324, DOI: 10.1007/s12307-011-0078-3, ISSN: 1875-2284.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21789687.
  • Sterling JA, Guelcher SA. Bone structural components regulating sites of tumor metastasis. Curr Osteoporos Rep. 2011 Jun; 9(2): 89-95. PMID: 21424744, PMCID: PMC3430076, DOI: 10.1007/s11914-011-0052-5, ISSN: 1544-2241.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21424744.
  • 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 [print-electronic]. 2011 Feb 2/1/2011; 71(3): 822-31. PMID: 21189326, PMCID: PMC3077118, PII: 0008-5472.CAN-10-2993, DOI: 10.1158/0008-5472.CAN-10-2993, ISSN: 1538-7445.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21189326.
  • 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 [print-electronic]. 2011 Jan; 48(1): 141-51. PMID: 20685406, PMCID: PMC2974944, PII: S8756-3282(10)01284-6, DOI: 10.1016/j.bone.2010.05.033, ISSN: 1873-2763.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20685406.
  • Sterling JA, Edwards JR, Martin TJ, Mundy GR. Advances in the biology of bone metastasis: how the skeleton affects tumor behavior. Bone [print-electronic]. 2011 Jan; 48(1): 6-15. PMID: 20643235, PII: S8756-3282(10)01358-X, DOI: 10.1016/j.bone.2010.07.015, ISSN: 1873-2763.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20643235.
  • 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. 2010; 5(11): e15451. PMID: 21085597, PMCID: PMC2981576, DOI: 10.1371/journal.pone.0015451, ISSN: 1932-6203.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21085597.
  • 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. 2006 Aug 8/1/2006; 66(15): 7548-53. PMID: 16885353, PII: 66/15/7548, DOI: 10.1158/0008-5472.CAN-06-0452, ISSN: 0008-5472.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16885353.
  • Sterling JA, Wu L, Banerji SS. PARP regulates TGF-beta receptor type II expression in estrogen receptor-positive breast cancer cell lines. Anticancer Res. 2006 May; 26(3A): 1893-901. PMID: 16827122, ISSN: 0250-7005.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16827122.