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 and the Immune System

For a long time my laboratory has been interested in the proliferation and differentiation of lymphocytes. Various studies led us to ask how lymphoid cells might interact with other cells in the bone marrow environment, the source of hematopoietic lymphoid cells. One set of cells that acts as an interloper in this environment is metastatic cancer cells. We have focused on metastatic, osteolytic, breast cancer cells that have a predeliction to metastasize to the bone marrow. A major research question is how the cancer cells affect the osteoblasts, cells which normally replace bone. Clinical studies indicated that bone lesions are normally not repaired in this situation. We asked if the osteoblasts are dysfunctional. In vitro, co-culture experiments of osteoblasts with osteolytic, metastatic breast cancer cells revealed an increase in the prevalence of apoptosis (programmed cell death) in the osteoblasts.

A second observation was that osteoblasts did not differentiate properly in the presence of breast cancer cells or their conditioned medium. The osteoblasts also underwent morphological change in the presence of the cancer cell conditioned medium.

We have also been examining the effects of exercise on the immune system. We have monitored phenotypes and mitogen responsiveness of blood lymphocytes from healthy young women during exercise training. We carried out a related study to determine how exercise may affect the restoration of lymphocytes, especially the CD4 T cell levels following chemotherapy for breast cancer. In both of these studies we explored possible mechanisms for observed changes in lymphocyte subpopulations and activation status such as cytokine levels and adhesion molecules. Some of these same approaches are being used to examine blood leukocytes from elderly individuals with marginal iron/zinc status (collaboration with Naman Ahluwalia, Nutrition).

Representative Publications:

• Gunes, H., Grove, D. S., Bour, B., Zawilla, S., and A. M. Mastro. 1993. The expression of forms of prolactin receptors in splenocytes and thymocytes of neonatal rats: The effect of milk ingestion. Endocrine Regulation 27, 193-200.
• Andrea M. Mastro, Carol V. Gay and Danny R. Welch 2003. The skeleton as a unique environment for breast cancer cells. J. Clin. Exper. Metastasis. 20: 275-284.
• Andrea M. Mastro, Carol V. Gay and Danny R. Welch 2003. The skeleton as a unique environment for breast cancer cells. J. Clin. Exper. Metastasis. 20: 275-284.
• Welch, Danny R., J. F. Harms, Andrea M. Mastro, Carol V. Gay and Henry J. Donahue. 2003 Breast Cancer metastasis to bone: Evolving Models and research challenges J. Muscoluskel. Neuron. Interact. 3: 30-38.
• Miles, M.P., William J. Kraemer, Bradley C. Nindl, Deborah S. Grove, Sharyn K. Leach, Keiichiro Dohi, James O. Marx, Jeff S. Volek and Andrea M. Mastro. 2003 Strength, workload, anaerobic intensity and the immunen response to resistance exercise in women Acta Physiol Scand 178: 155-163.
• Donahue, Henry J., Marnie M. Saunders, Zhongyong Li, Andrea M. Mastro, Carol V. Gay and Danny R. Welch. 2003 Intercellular Communication in Breast Cancer Metastasis to Bone. J. Musculoskel. Neuron. Interact. 3: 156-161.

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