Appalachian Student Research Forum

                                Centre at Millennium Park  •  Johnson City, TN

Keynote Speaker:

M. Sharon Stack, Ph.D.

Professor and Vice-Chair for Research Mulligan Endowed Professor of Cancer Research Department of Pathology & Anatomical Sciences University of Missouri, Columbia

B.S. Clemson University, Biochemistry 1981 Fulbright Scholar, Universitat Bonn, Germany 1982 M.S. Biomedical Science/Biochemistry, East Tennessee State University 1985 Ph.D. Biochemistry, University of Louisville  1989 Post-Doctoral Research Associate, Duke University 1989-1991 Assistant Research Professor, Duke University 1991-1994 Assistant Professor, Associate Professor with Tenure, Professor, Northwestern University 1994-2006 Professor and Vice-Chair for Research, University of Missouri, 2007-present

Keynote Address Abstract

Proteinase Regulation in the Ovarian Tumor Microenvironment

The ability to invade host tissues and metastasize is the major cause of cancer-related death.  During tumor invasion, metastasizing cells disrupt normal cell-cell and cell-matrix contacts and acquire a migratory, invasive phenotype.  Subsequent alterations in cellular architecture mediated by modified extracellular matrix (ECM) attachments induce expression of proteinases that degrade ECM proteins, facilitating migration through the modified tissue to establish metastatic foci.  Epithelial ovarian carcinoma is the leading cause of death from gynecologic malignancy, as 75% of women with this disease succumb to complications resulting from disseminated intra-peritoneal metastasis. The initiating events in the development of ovarian carcinoma are poorly understood. However, ovarian carcinoma has an unique metastatic mechanism requiring reversible modulation of cell-cell and cell-ECM contacts that involves shedding of cells from the primary tumor followed by subsequent intra-peritoneal adhesion, invasion and proliferation. Unlike most highly metastatic tumors, the majority of women with advanced intraperitoneal disease have no clinically apparent lymphatic or hematogenous metastases, implying that a novel mechanism for metastasis is operative in ovarian cancer.  Further, as metastases are largely confined to the peritoneal cavity, microenvironmental factors that modulate intraperitoneal adhesion, motility and invasion play a predominant role in ovarian pathobiology.  Ongoing research utilizes an integrative approach involving examination of 2-dimensional (2D) and 3D tissue culture systems complemented by murine tumor models and analyses of human tumors.  Understanding the molecular mechanisms by which tumor cells orchestrate multiple microenvironmental cues to regulate the expression and activity of these metastasis-associated proteinases is the major focus of the laboratory.