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Michael Bromberg, MD, PhD

Interim Chief, Section of Medical Oncology

Professor, Medicine

Professor, Sol Sherry Thrombosis Research Center

Professor, Pharmacology

Telephone:  215-707-4403

Fax:  215-707-2783

Email: mbromber@temple.edu

Department of Medicine, Section of Hematology

Department of Medicine, Section of Oncology

Sol Sherry Thrombosis Research Center

Department of Pharmacology

University of Delaware, Newark, DE

1974-1978, B.S., Chemistry

 

Temple University, Philadelphia, PA

1978-1984, Ph.D., Pharmacology

 

Temple University School of Medicine, Philadelphia, PA

1984-1988, M.D., Medicine

 

Temple University Hospital, Philadelphia, PA

1988-1991, Intern and Resident in Internal Medicine

 

Yale University School of Medicine, New Haven, CT

1991-1995, Hematology and Oncology Fellow

 

Yale University School of Medicine, New Haven, CT

1993-1995, Research Fellow (Lab. of  W. H. Konigsberg, PhD)

 

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My laboratory examines the molecular mechanisms that promote tumor growth and metastasis and specifically focuses on the role of tissue factor (TF) in these processes.   TF is a 47 kDa transmembrane glycoprotein that complexes with factor VII/VIIa to initiate blood coagulation.  Studies carried out in our laboratory and by others have shown that a wide variety of tumor cells express TF.   We showed that transfection with the cDNA encoding human TF increased the metastatic potential of a human melanoma cell line with low endogenous expression of TF and low metastatic potential in immunocompromised mice. These results indicated that TF promotes tumor metastasis.   Further studies by our laboratory have shown that both the cytoplasmic domain of the molecule, which is not involved in blood coagulation, and the extracellular domain, in which procoagulant activity is localized, are required for the full metastatic effect of TF. However, the mechanism by which TF promotes metastasis is not fully understood.

We are currently examining the functions of extracellular and cytoplasmic domains of TF in metastasis as well as determining the step(s) in the metastatic pathway that are promoted by TF. TF has also been implicated in the process of angiogenesis, a critical step in the metastatic pathway. Other laboratories have shown a regulatory interaction between TF and vascular endothelial cell growth factor (VEGF). Our other area of investigation involves the interaction between TF and VEGF. Specifically, we are examining whether TF and VEGF function in an autocrine fashion, whereby VEGF secreted by a tumor activates the VEGF receptors of tumor cells to induce TF expression, increase cell motility, and enhance tumor growth and metastatic potential. These studies involving the mechanism by which TF promotes tumor progression and the interaction between TF and VEGF might provide for the development of novel strategies to prevent tumor growth and inhibit metastasis.

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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

22496089. Singhal A, Karachristos A, Bromberg M, Daly E, Maloo M, Jain AK, Hypercoagulability in end-stage liver disease: prevalence and its correlation with severity of liver disease and portal vein thrombosis. Clin Appl Thromb Hemost 18:6(594-8)2012 Nov

20490335. Sebastiano C, Bromberg M, Breen K, Hurford MT, Glanzmann's thrombasthenia: report of a case and review of the literature. Int J Clin Exp Pathol 3:4(443-7)2010 Apr 25

19966052. Khan MM, Liu Y, Khan ME, Gilman ML, Khan ST, Bromberg M, Colman RW, Upregulation of tissue factor in monocytes by cleaved high molecular weight kininogen is dependent on TNF-alpha and IL-1beta. Am J Physiol Heart Circ Physiol 298:2(H652-8)2010 Feb

19483730. Liu Y, Pixley R, Fusaro M, Godoy G, Kim E, Bromberg ME, Colman RW, Cleaved high-molecular-weight kininogen and its domain 5 inhibit migration and invasion of human prostate cancer cells through the epidermal growth factor receptor pathway. Oncogene 28:30(2756-65)2009 Jul 30

18612547. Jiang X, Zhu S, Panetti TS, Bromberg ME, Formation of tissue factor-factor VIIa-factor Xa complex induces activation of the mTOR pathway which regulates migration of human breast cancer cells. Thromb Haemost 100:1(127-33)2008 Jul

17337598. Avraamides C, Bromberg ME, Gaughan JP, Thomas SM, Tsygankov AY, Panetti TS, Hic-5 promotes endothelial cell migration to lysophosphatidic acid. Am J Physiol Heart Circ Physiol 293:1(H193-203)2007 Jul

17050888. Bromberg ME, Immune thrombocytopenic purpura--the changing therapeutic landscape. N Engl J Med 355:16(1643-5)2006 Oct 19

16894464. Jiang X, Guo YL, Bromberg ME, Formation of tissue factor-factor VIIa-factor Xa complex prevents apoptosis in human breast cancer cells. Thromb Haemost 96:2(196-201)2006 Aug

14717972. Jiang X, Bailly MA, Panetti TS, Cappello M, Konigsberg WH, Bromberg ME, Formation of tissue factor-factor VIIa-factor Xa complex promotes cellular signaling and migration of human breast cancer cells. J Thromb Haemost 2:1(93-101)2004 Jan

11959915. Song X, Wang B, Bromberg M, Hu Z, Konigsberg W, Garen A, Retroviral-mediated transmission of a mouse VL30 RNA to human melanoma cells promotes metastasis in an immunodeficient mouse model. Proc Natl Acad Sci U S A 99:9(6269-73)2002 Apr 30

11816709. Bromberg ME, Bailly MA, Konigsberg WH, Role of protease-activated receptor 1 in tumor metastasis promoted by tissue factor. Thromb Haemost 86:5(1210-4)2001 Nov

10456459. Bromberg ME, Sundaram R, Homer RJ, Garen A, Konigsberg WH, Role of tissue factor in metastasis: functions of the cytoplasmic and extracellular domains of the molecule. Thromb Haemost 82:1(88-92)1999 Jul

10367166. Bromberg ME, Cappello M, Cancer and blood coagulation: molecular aspects. Cancer J Sci Am 5:3(132-8)1999 May-Jun

9609244. Donnelly KM, Bromberg ME, Milstone A, Madison McNiff JM, Terwilliger G, Konigsberg WH, Cappello M, Ancylostoma caninum anticoagulant peptide blocks metastasis in vivo and inhibits factor Xa binding to melanoma cells in vitro. Thromb Haemost 79:5(1041-7)1998 May

7667269. Bromberg ME, Konigsberg WH, Madison JF, Pawashe A, Garen A, Tissue factor promotes melanoma metastasis by a pathway independent of blood coagulation. Proc Natl Acad Sci U S A 92:18(8205-9)1995 Aug 29

21043906. Bromberg ME, Sevy RW, Salganicoff L, (45)Ca efflux and agonist induced changes in force in a model of thrombin activated platelets. Platelets 3:3(137-44)1992

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