In the past ten years, I have built a research program based on studies of the molecular processes regulating prostate tumor cell invasion and metastases. Much of our work has focused on understanding IL-10 receptor regulation and signaling pathways modulating the Tissue Inhibitor of Metalloproteinase I and Matrix Metalloproteinase 2 expression in human prostate cancer cells in vitro and in vivo. The overall objective is to assess the effect of IL-10 on gene expression in relationship to preventing tumor growth and metastasis in a SCID mouse xenograph model.

In the past 4 years, I have broadened the scope of my work on prostate cancer and expanded in the newly emerging field of 'proteomics' and gene discovery. My laboratory has developed a unique 'proteomics based gene discovery platform' for identification of novel "DNA-binding proteins" (i.e. transcription factors, signal molecules). Basically, we have developed a 'high through put' screening method for processing thousands of double stranded DNA sequences, which bind novel nuclear proteins. By comparisons of proteins isolated from normal, benign, pre-malignant and malignant tissue from human prostate, we have been able to isolate and clone several previously unknown regulatory proteins. The work has resulted in three significant accomplishments, including:

(1) the development of a diagnostic marker for prostate cancer (i.e. PCAM-1) which is significantly better than PSA (e.g. 30% more sensitive and 40% more specific) , the current clinical assay for prostate cancer.

(2) the development of a new therapeutic methodology utilizing 'DNA ZYMs' oligonucleotides (a modified ribozyme technology which produces more stable and efficacious oligos).

(3) The demonstration that 'PCAM-1 DNA ZYM-1' treatment of pre-clinical animal model tumors can efficiently target and eradicate prostate tumors (n=45/50 tumors).

This work represents a significant contribution to the development of a broad based methodology for identifying nuclear proteins critical to tumor survival (the approach should be adaptable to studies on other tumors as well).

Selected Publications:

Stearns, M.E. and Wang, M. Type IV Collagenase (72 KDa) Expression in Human Prostate: Benign and Malignant Tissue. Cancer Res., 53:878-883, 1993.

Wang, M and Stearns, M.E. Isolation and characterization of PC-3 human prostatic tumor sublines which preferentially metastasize to select organs in s.c.i.d. mice. Differentiation, 48: 115-125, 1991.

Wang, M. Hu, Y., Shima, I. and Stearns, M.E. Identification of positive and negative regulator elements for the Tissue Inhibitor of Metalloproteinase 1 gene. Oncol. Res. 10:219-233, 1998.

Stearns, M.E. and Wang, M. Alendronate Blocks Metalloproteinase Secretion and Bone Collagen 1 Release by PC-3 ML cells in SCID mice. Clin. And Exp. Metastasis, Vol. 16, #6, 693-702, 1998.

Stearns, M.E., Garcia, F.U., Fudge, K. A and Wang, M. Role of IL-10 and TGF-1 in the Angiogenesis and Metastasis of prostate primary tumor lines from orthotopic implants in SCID mice. Cancer Res. 5:711-720, 1999.

Fuqua, S.A.W., McDonnell, D.P., Russo, J., Shackney, S.E. and Stearns, M.E. Estrogen, estrogen receptors and selective estrogen receptor modulators in human breast cancer. Women in Cancer. 2: 21-32, 2000.