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Jennifer Koblinski, PhD
Assistant Professor of Pathology
Lurie 4-105
303 E. Chicago Avenue
Chicago, IL 60611
j-koblinski@northwestern.edu
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Phone: (312) 503-0794
Fax: (312) 503-0095
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Medical School
Wayne State University (PhD)
Site of Fellowship
NIH, National Institute of Dental and Craniofacial Research
Research Interests
As many as 20% of breast cancer patients have brain metastases, with women surviving only 2-16 months after diagnosis of this metastasis. Thus, resolving the mechanisms of metastasis to the brain is clinically important. In invasive breast carcinomas, Syndecan (Sdc) 1 is observed in stromal fibroblasts and endothelial cells where it is involved in tumor growth and angiogenesis. Staining for Sdc1 in both the tumor and stromal cells has been reported to be a negative predictor of disease free and overall survival in estrogen receptor (ER) negative breast tumors, and expression of Sdc1 and 4 is associated with increased proliferation index in breast tumors. A direct connection between these receptors and breast cancer metastasis has not been shown. The reduced expression of Sdc1 or 4 in MDA-231 breast cancer cells and reduced expression of Sdc4 in CN34Brm breast cancer cells significantly decreased metastases to only the brain but had no effect on bone, lung, or ovarian metastases when the cells were injected into the left ventricle of the mouse heart (nude mice). Additionally, metastases to the brain was reduced when these cells were injected in the orthotopic site of NSG mice, however, primary tumor growth and metastases to the lung, liver, ovaries, and lymph nodes were not affected in this model. These results suggest Sdc1 and 4 facilitate breast cancer organotropism to the brain. We are currently examining the mechanism of how Sdc1 and 4 affects breast cancer organotorpism to the brain. These results may explain the correlative observations of Sdc expression with poor clinical outcome. These studies may lead to development of new biomarkers and/or treatment for breast cancer metastasis to the brain.
Selected Publications
Campo McKnight DA, Sosnoski DM, Koblinski JE, Gay CV Roles of osteonectin in the migration of breast cancer cells into bone. J. Cell. Biochem. 97:288-302, 2006.
Koblinski JE, Kaplan-Singer B, VanOsdol S, Wu M, Engbring JE, Wang S, Goldsmith C, Piper JT, Vostal JG, Harms J, Welch D, Kleinman H. Endogenous osteonectin/SPARC/BM-40 expression inhibits MDA-MB-231 breast cancer metastasis. Cancer Res. 65:7370-7377, 2005.
Koblinski JE, Wu M, Demeler B, Jacob K, Kleinman H. Matrix cell adhesion molecule activation by various. J Cell Sci 118: 2965-74, 2005.
Munshi HG, Wu YI, Mukhopadhyay S, Ottaviano AJ, Sassano A, Koblinski JE, Platanias LC, Stack MS. Differential regulation of membrane type 1-matrix metalloproteinase activity by ERK 1/2- and p38 MAPK-modulated tissue inhibitor of metalloproteinases 2 expression controls transforming growth factor-beta1-induced pericellular collagenolysis. J Biol Chem. 279:39042-50, 2004
Engbring JA, Hossain R, VanOsdol S, Kaplan-Singer B, Wu M, Hibino S, Koblinski JE. The laminin a-1 chain peptide, AG73, increases fibronectin levels in breast and melanoma cancer cells. Clin Exp Metastasis 25: 241-52, 2008.
Malinda KM, Wysocki AB, Koblinski JE, Kleinman HK, Ponce ML. Angiogenic laminin-derived peptides stimulate wound healing. Int J Biochem Cell Biol 40:2771-80, 2008
Rempel SA, Hawley RC, Gutiérrez JA, Mouzon E, Bobbitt KR, Lemke N, Schultz C, Schultz LR, Golembieski W, Koblinski JE, VanOsdol S, Miller CG. Splenic and immune alterations of the Sparc-null mouse accompany a lack of immune response. Genes Immun 8:262-74, 2007.
View more Publications by Jennifer Koblinski, PhD
listed in the National Library of Medicine (PubMed)
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