Department of Laboratory Medicine and Pathology
Johns Hopkins, 1984, Ph.D.
Ovarian cancer; diagnostic markers; cell-cell interactions
Dr. Skubitz’s research is focused on the interaction of ovarian cancer cells with adhesion molecules present in the extracellular matrix and elsewhere, as well as with cell-cell interactions. We are interested in determining how ovarian cancer spreads, its genetic profile, and new biomarkers. Ovarian epithelial cancer cells do not adhere normally to the basement membrane; rather, they release from the basement membrane, seed other sites, develop into an ascitic form, or invade into the stroma of the ovary. We have shown that the more aggressive behavior of the malignant ovarian carcinoma cells, compared to normal ovarian epithelial cells, correlates with alterations in laminin receptors, in particular the a6b4 integrin. We have defined a mechanism whereby ovarian carcinoma cells adhere to mesothelial cells that line the peritoneal cavity, and then invade into the underlying tissues. We have discovered that the b1 integrin subunits and CD44 on the surface of ovarian carcinoma cells interact with mesothelial cells and their associated extracellular matrix, thereby promoting ovarian carcinoma cell adhesion and migration. We have shown that these same molecules play a role in promoting the invasion, spreading, and proliferation of ovarian carcinoma cells in vitro using single cells, multicellular aggregates or spheroids, and ovarian cancer cells isolated from the ascites fluid of patients. In order to identify novel biomarkers and/or therapeutic targets for ovarian cancer, as well as other types of cancer, we have analyzed Affymetrix gene microarray expression data and discovered many genes to be differentially expressed between cancer tissues and their normal tissue counterparts. In the case of the ovarian cancer genes, we have validated the data by immunohistochemistry and identified several potential biomarkers. Furthermore, we have been making strides to identify novel serum biomarkers that will ultimately improve the diagnostic assays for ovarian cancer. Namely, we are using the complementary proteomic techniques of DIGE, iTRAQ, and mass spectrometry protein profiling to discover proteins that are differentially expressed in the blood of ovarian cancer patients compared to the blood of control women. In summary, these research studies represent an approach toward understanding the molecular mechanisms modulating the phenotypic behavior of cancer cells and potentially aid in designing biomarkers and/or biopharmaceuticals for therapeutic use in cancer
- Skubitz, K.M., Zimmerman, W., Kammerer, R., Pambuccian, S., and Skubitz, A.P.N. 2006. Differential gene expression identifies subgroups of renal cell carcinoma. Journal of Laboratory and Clinical Medicine 147:250-267.
- Burleson, K.M., Boente, M.P., Pambuccian, S.E., and Skubitz, A.P.N. 2006. Disaggregation and invasion of ovarian carcinoma ascites spheroids. Journal of Translational Medicine 4:6.
- Skubitz, K.M., Cheng, E.Y., Clohisy, D.R., Thompson, R.C., and Skubitz, A.P.N. 2005. Differential gene expression in liposarcoma, lipoma, and adipose tissue. Cancer Investigation 23:105-118.
- Iida, J., Skubitz, A.P.N., McCarthy, J.B., and Skubitz, K.M. 2005. Protein kinase activity is associated with CD63 in melanoma cells. Journal of Translational Medicine 3:42-50.
- Skubitz, K.M. and Skubitz, A.P.N. 2004. Gene expression in aggressive fibromatosis. Journal of Laboratory and Clinical Medicine 143:89-98.
- Burleson, K.M., Casey, R.C., Skubitz, K.M., Pambuccian, S.E., Oegema, T.R., and Skubitz A.P.N. 2004. Ovarian carcinoma ascites spheroids adhere to extracellular matrix components and mesothelial cell monolayers. Gynecologic Oncology 93:170-181.
- Hibbs, K., Skubitz, K.M. Pambuccian, S., Casey, R.C., Burleson, K.M., Oegema, T., Jr., Thiele, J.J., Grindle, S.M., Bliss, R., and Skubitz, A.P.N. 2004. Differential gene expression in ovarian carcinoma: Identification of potential biomarkers. American Journal of Pathology 165(2):397-414.
- Skubitz, K.M. and Skubitz, A.P.N. 2004. Characterization of sarcomas by means of gene expression. Journal of Laboratory and Clinical Medicine 144:78-91.
- Skubitz, K.M., Cheng, E.Y., Clohisy, D.R., Thompson, R.C., and Skubitz, A.P.N. 2004. Gene expression in giant-cell tumors. Journal of Laboratory and Clinical Medicine 144:193-200.
- Burleson, K.M., Hansen, L.K., Skubitz, A.P.N. 2004. Ovarian carcinoma spheroids disaggregate on type I collagen and invade live human mesothelial cell monolayers. Clinical & Experimental Metastasis 21:685-697.
- Casey, R.C., Oegema Jr., T.R., Skubitz, K.M., Pambuccian, S.E., Grindle, S.M., and Skubitz, A.P.N. 2003. Cell membrane glycosylation mediates the adhesion, migration, and invasion of ovarian carcinoma cells. Clinical and Experimental Metastasis 20:143-152.
- Casey, R.C., Koch, K.A.,Oegema, T.R., Jr., Skubitz, K.M., Pambuccian, S.E., Grindle, S.M., and Skubitz, A.P.N. 2003. Establishment of an in vitro assay to measure the invasion of ovarian carcinoma cells through mesothelial cell monolayers. Clinical and Experimental Metastasis 20:343-356.
- Skubitz, K.M. and Skubitz, A.P.N. 2003. Differential gene expression in uterine leiomyoma. Journal of Laboratory and Clinical Medicine 141:297-308.
- Skubitz, K.M. and Skubitz, A.P.N. 2003. Differential gene expression in leiomyosarcoma. Cancer 98:1029-1038.
- Skubitz, K.M. and Skubitz, A.P.N. 2002. Differential gene expression in renal-cell cancer. Journal of Laboratory and Clinical Medicine 140:52-64.
- Casey, R.C., Burleson, K.M., Skubitz, K.M., Pambuccian S.E., Oegema, T.R. Jr., Ruff, L.E., and Skubitz, A.P.N. 2001. b1-integrins regulate the formation and adhesion of ovarian carcinoma multicellular spheroids. American Journal of Pathology 159:2071-2080.
Last modified on: August 8, 2006