Andrea M. Mastro Professor of Microbiology and Cell Biology 431 South Frear Laboratory, University Park, PA 16802 Phone:(814) 863-0152 Fax: (814) 863-7024 Email: a36@psu.edu B.A. in biology, Carlow College Ph.D. in biology, Pennsylvania State University Mastro Lab Web Site

Breast Cancer Metastatsis; Diet, Exercise and the Immune System

A. Metastatic Breast Cancer and the Bone Microenvironment

Our laboratory focuses on the interaction of breast cancer cells with bone. Breast cancer cells frequently metastasize to the skeleton and bring about bone loss.  A major research question is how the osteoblasts, the cells that normally replace bone, are affected by the cancer cells. We have carried out both cell culture and in vivo studies, and found that metastatic breast cancer cells lead to an increase in osteoblast apoptosis and a loss of their ability to produce bone matrix proteins.  In contrast the osteoblasts develop a stress response and produce pro-inflammatory cytokines, i.e. IL-6, IL-8, MCP-1, as well as VEGF.  These molecules play a role in recruiting osteoclasts, the cells that directly degrade bone. We have also examined the interaction of cancer and osteoblasts in a novel  3-D model.  In this system, the breast cancer cells attach to and penetrate through the osteoblast tissue, modify the osteoblast organization and the extracellular matrix, and align in an “Indian filing” manner seen in vivo but usually not in cell cuture.

B. Diet, exercise and immunity

Our laboratory has also maintained an interest in how exercise and diet affect the immune system.  We have monitored phenotypes and mitogen responsiveness of blood lymphocytes from healthy young women, from women following chemotherapy, and from elderly individuals with marginal iron/zinc status. In a current study the changes in lymphocyte subpopulations with a protein supplemented diet are being examined (collaboration J. Volek, W. Kraemer, Univ Conn).

Representative Publications:

• Hutnick, N.A., N.I. Williams, W.J. Kraemer, E. Orsega-Smith, R.H. Dixon, A.D. Bleznak, A.M. Mastro. 2005. Exercise and lymphocyte activation following chemotherapy for breast cancer. Medicine and Science in Sports and Exercise. 37: 1827-1835.

• Phadke, P.A., R.R. Mercer, J.F. Harms, Y. Jia, J.C. Kappes, A.R. Frost, J.L. Jewell, K.M. Bussard, S. Nelson, C. Moore, C.V. Gay, A.M. Mastro and D.R. Welch. 2006. Kinetics of metastatic breast cancer cell trafficking in bone. Clin. Canc. Res., 12: 1431-1440.

• Bussard, K.M., C.V. Gay, and A.M. Mastro. 2008.  The Bone Microenvironment in Metastasis:  What Is Special About Bone?  Cancer Metastasis Reviews 27:41-55.

• Kinder, E. Chislock, K.M. Bussard, L. Shuman, and A.M. Mastro.  2008.  Metastatic breast cancer induces an osteoblast inflammatory response.  Exp Cell Res 314: 173-183.

• Dhurjati, R,  Krishnan,, V L. A. Shuman, A. M. Mastro, E. A. Vogler. 2008. Metastatic breast cancer cell colonization degrades three-dimensional osteoblastic tissue in vito. Clin Exp Met  25:741-752

• Mastro, A.M. , E. A. Vogler. 2009. A 3D Osteogenic-Tissue Model for the Study of Metastatic Tumor-Cell Interactions with Bone. Cancer Research, in press.

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