Angela Drew, Ph.D.
Dept. of Molecular Oncogenesis
2180 E. Galbraith Rd.
Cincinnati, OH 45237

Email Angela

Funding
Publications

My lab investigates factors related to ovarian cancer metastasis. Ovarian cancer is an insidious disease with a disproportionately high mortality rate compared with other tumor types. The reasons for this may lie in the late stage of diagnosis, and in the rapid development of chemotherapy resistance for many patients. There are currently large gaps in knowledge of the early events in tumor spread and of tumor utilization of host mechanisms that facilitate dissemination.
Our group focuses on inflammation and metalloproteases and their effects on tumor metastasis, in vivo. The role of membrane-associated metalloproteases is currently being investigated through in vitro genetic manipulation of ovarian carcinoma cell lines and patient samples, and subsequent implantation in various mouse metastasis models. While broad spectrum inhibition of metalloproteases did not reduce metastasis in patients in clinical trials, highly specific targeting of individual metalloproteases has shown much promise. We are focusing specifically on membrane-bound metalloproteases since our earlier work has shown they are influential on ovarian cancer progression.
In addition, we have previously shown that inflammation plays an important role in driving the spread of ovarian tumors, though the mediators are still not known. We are using transgenic mouse approaches to determine the contribution of an inflammatory protein called interleukin-6 (IL-6) and its receptor (IL-6Rα) to the progression of ovarian cancer. Despite being a growth factor for tumor cells, blocking the receptor with an antibody increases metastatic spread. Since both tumor and inflammatory cells produce both IL-6 and the receptor, the contribution of each must be assessed to determine the best means of intervention. It is our aim to find specific targets that can abrogate the spread of tumors in vivo.
The translational direction of our work is greatly enhanced by strong collaborations with UC clinicians with expertise in gynecologic oncology and pathology. This teamwork approach provides great opportunities for viewing metastasis both broadly and specifically as a target for altering tumor prognosis.



Funding Support
American Cancer Society, Research Scholar Grant, 2006 (PI)
Title: Interleukin-6 and ovarian Cancer Metastasis.

American Cancer Society, Ohio Division Supported Research Grant, 2005 (PI)
Title: Role of inflammation in Ovarian Cancer.

Faculty Research Support Program, University of Cincinnati Research Council, 2005 (PI)
Title: ‘Inflammation and Metastasis of Ovarian Cancer’.

Cancer Center Pilot Grant Program, University of Cincinnati Cancer Center, 2004 (PI)
Title: ‘Role of the MT1-MMP-VEGF Axis on the Development and Spread of Ovarian Cancer’.

RWH Project Grant, Royal Women’s Hospital, Melbourne, Australia, 2002 (PI)
Title: ‘The Role of Metalloproteases in Ovarian Tumor Metastasis’.

Howard Florey Centenary Fellowship, NH&MRC, Australia, 2001 (PI)
Title: ‘Involvement of MT1-MMP in Cellular Migration and Extravasation’.

Post-doctoral Fellowship, American Heart Association, Ohio Valley Affiliate, 1998 (PI)
Title: ‘Role of Fibrinogen and Plasminogen in Neointima Formation in gene-targeted Mice’.



Publications

1:	Robinson-Smith TM, Isaacsohn I, Mercer CA, Zhou M, Van Rooijen N, Husseinzadeh N, McFarland-Mancini MM, Drew AF Macrophages mediate inflammation-enhanced metastasis of ovarian tumors in mice. Cancer Res. 2007 Jun;67(12):5708-16. PMID: 17575137 [PubMed - indexed for MEDLINE]

2:	Wang X, Bao X, McFarland-Mancini M, Isaacsohn I, Drew AF, Smithrud DB Investigation of the intracellular delivery of fluoresceinated peptides by a host-[2]rotaxane. J Am Chem Soc. 2007 Jun;129(23):7284-93. PMID: 17516642 [PubMed - indexed for MEDLINE]

3:	Bao X, Isaacsohn I, Drew AF, Smithrud DB Determining the binding and intracellular transporting abilities of a host-[3]rotaxane. J Org Chem. 2007 May;72(11):3988-4000. PMID: 17477574 [PubMed - indexed for MEDLINE]

4:	Bao X, Isaacsohn I, Drew AF, Smithrud DB Determining the intracellular transport mechanism of a cleft-[2]rotaxane. J Am Chem Soc. 2006 Sep;128(37):12229-38. PMID: 16967974 [PubMed - indexed for MEDLINE]

5:	Drew AF, Blick TJ, Lafleur MA, Tim EL, Robbie MJ, Rice GE, Quinn MA, Thompson EW Correlation of tumor- and stromal-derived MT1-MMP expression with progression of human ovarian tumors in SCID mice. Gynecol Oncol. 2004 Dec;95(3):437-48. PMID: 15581944 [PubMed - indexed for MEDLINE]

6:	Lafleur MA, Drew AF, de Sousa EL, Blick T, Bills M, Walker EC, Williams ED, Waltham M, Thompson EW Upregulation of matrix metalloproteinases (MMPs) in breast cancer xenografts: a major induction of stromal MMP-13. Int J Cancer. 2005 Apr;114(4):544-54. PMID: 15551360 [PubMed - indexed for MEDLINE]

7:	Drew AF, Tucker HL, Liu H, Witte DP, Degen JL, Tipping PG Crescentic glomerulonephritis is diminished in fibrinogen-deficient mice. Am J Physiol Renal Physiol. 2001 Dec;281(6):F1157-63. PMID: 11704568 [PubMed - indexed for MEDLINE]

8:	Degen JL, Drew AF, Palumbo JS, Kombrinck KW, Bezerra JA, Danton MJ, Holmbäck K, Suh TT Genetic manipulation of fibrinogen and fibrinolysis in mice. Ann N Y Acad Sci. 2001 ;936():276-90. PMID: 11460484 [PubMed - indexed for MEDLINE]

9:	Drew AF, Liu H, Davidson JM, Daugherty CC, Degen JL Wound-healing defects in mice lacking fibrinogen. Blood. 2001 Jun;97(12):3691-8. PMID: 11389004 [PubMed - indexed for MEDLINE]

10:	Hattori N, Degen JL, Sisson TH, Liu H, Moore BB, Pandrangi RG, Simon RH, Drew AF Bleomycin-induced pulmonary fibrosis in fibrinogen-null mice. J Clin Invest. 2000 Dec;106(11):1341-50. PMID: 11104787 [PubMed - indexed for MEDLINE]

11:	Palumbo JS, Kombrinck KW, Drew AF, Grimes TS, Kiser JH, Degen JL, Bugge TH Fibrinogen is an important determinant of the metastatic potential of circulating tumor cells. Blood. 2000 Nov;96(10):3302-9. PMID: 11071621 [PubMed - indexed for MEDLINE]

12:	Drew AF, Tucker HL, Kombrinck KW, Simon DI, Bugge TH, Degen JL Plasminogen is a critical determinant of vascular remodeling in mice. Circ Res. 2000 Jul;87(2):133-9. PMID: 10903997 [PubMed - indexed for MEDLINE]

13:	Drew AF, Schiman HL, Kombrinck KW, Bugge TH, Degen JL, Kaufman AH Persistent corneal haze after excimer laser photokeratectomy in plasminogen-deficient mice. Invest Ophthalmol Vis Sci. 2000 Jan;41(1):67-72. PMID: 10634603 [PubMed - indexed for MEDLINE]

14:	Bugge TH, Lund LR, Kombrinck KK, Nielsen BS, Holmbäck K, Drew AF, Flick MJ, Witte DP, Danø K, Degen JL Reduced metastasis of Polyoma virus middle T antigen-induced mammary cancer in plasminogen-deficient mice. Oncogene. 1998 Jun;16(24):3097-104. PMID: 9671388 [PubMed - indexed for MEDLINE]

15:	Drew AF, Kaufman AH, Kombrinck KW, Danton MJ, Daugherty CC, Degen JL, Bugge TH Ligneous conjunctivitis in plasminogen-deficient mice. Blood. 1998 Mar;91(5):1616-24. PMID: 9473227 [PubMed - indexed for MEDLINE]

16:	Carmeliet P, Moons L, Lijnen R, Baes M, Lemaître V, Tipping P, Drew A, Eeckhout Y, Shapiro S, Lupu F, Collen D Urokinase-generated plasmin activates matrix metalloproteinases during aneurysm formation. Nat Genet. 1997 Dec;17(4):439-44. PMID: 9398846 [PubMed - indexed for MEDLINE]

17:	Drew AF, Davenport P, Apostolopoulos J, Tipping PG Tissue factor pathway inhibitor expression in atherosclerosis. Lab Invest. 1997 Oct;77(4):291-8. PMID: 9354763 [PubMed - indexed for MEDLINE]

18:	Drew AF, Tipping PG T helper cell infiltration and foam cell proliferation are early events in the development of atherosclerosis in cholesterol-fed rabbits. Arterioscler Thromb Vasc Biol. 1995 Oct;15(10):1563-8. PMID: 7583528 [PubMed - indexed for MEDLINE]

19:	Drew AF, Tipping PG Cyclosporine treatment reduces early atherosclerosis in the cholesterol-fed rabbit. Atherosclerosis. 1995 Aug;116(2):181-9. PMID: 7575773 [PubMed - indexed for MEDLINE]