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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
Our laboratory studies the role of matrix proteins in breast cancer metastasis to bone. Approximately 60-70% of breast cancer patients who have died or are dying of breast cancer have bone metastases. Therefore, resolving the mechanisms of metastasis to bone is of critical importance. Laminin-1 (?1?1?1), a major basement membrane matrix glycoprotein, is involved in normal and neoplastic breast biology, and enhances adhesion, migration, and metastasis of tumor cells. Laminin-1 is cleaved in the tumor environment and synthetic laminin-derived peptides alter the biology of tumor cells. The peptide, AG73 (RKRLQVQLSIRT, laminin-?1 chain 2716-2731), promotes tumor growth and metastasis. We have found that AG73 significantly increases brain and bone metastases of MDA-231 breast carcinoma cells in an intracardiac metastasis model. The tumors in the bone of these mice treated with AG73 were also larger than the control group. We hypothesized that AG73 increases arrival of the tumor cells to the bone and brain and/or increases growth of the breast cancer cells in these organs. We are now investigating whether arrival of these cells to the both bone and brain is increased, in vivo, in AG73-treated mice compared to control-treated mice. In addition, experiments to identify the receptor for AG73 on breast cancer cells and its signaling pathway are currently underway. Gene array analysis has allowed us to identify genes which are up- and down-regulated by AG73 in MDA-231 breast cancer cells. The ultimate goal is to identify genes that regulate breast cancer metastasis to bone and brain for potential diagnostic and therapeutic treatments.
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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