Journal of Biotechnology & Biomaterials
Open Access

Abstract

Cancer is currently one of the most prevalent causes of human deaths in the world. Current therapeutic options aim only to slow the progression of cancer disease. Th erefore, a renewed eff ort must be made to identify relevant endogenous cancer inhibitors that could be exploited as therapeutic drugs. We identifi ed several endogenous anti-cancer molecules, which are released from extracellular matrix (ECM) into the blood circulation of cancer patients. Several of these endogenous circulating molecules were cloned and identifi ed as angioinhibitors of tumor growth. Th ese endogenous angioinhibitory proteins bind to the cell surface integrins and transduce the signalling mechanisms & regulate angiogenesis. Th us, integrins serve as transmembrane linkers between the ECM and cytoskeleton for outside-in signalling. One such endogenous circulating molecule, tumstatin, a 28-kDa protein from the C-terminal non-collagenous (NC1) domain of alpha3 type IV collagen was identifi ed as an inhibitor of angiogenesis. Tumstatin interacting with alphaVbeta3 integrin and inhibits activation of focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI-3K), serine/threonine kinase (Akt/protein kinase B), mammalian target of rapamycin (mTOR) and prevents dissociation of eukaryotic translation initiation factor 4E (eIF4E) from 4E binding protein (4E-BP1) leading to the inhibition of Cap-dependent translation in proliferating endothelial cells. Tumstatin when interacting with alpha3beta1 integrin it inhibits alphaVbeta3 integrin transdominantly and inhibits hypoxia induced pro-infl ammatory cyclo-oxygenase-2 (COX-2) expression and tumor angiogenesis and tumor growth. In addition adenovirus secreting tumstatin exhibited signifi cant inhibition of laser induced CNV in mice and MMP-2 activation invitro and in-vivo.

Biography

SudhakarAkul is the founder Director of Cell Signaling, Retinal and Tumor Angiogenesis Laboratory at Boys Town National Research Hospital, Associate Professor at Creighton University School of Medicine and University of Nebraska Medical Center, Omaha, NE, USA. He did his postdoctoral training at Harvard Medical School, Boston, MA, USA (2003). He has received Ph.D (2001), M.Phill (1997) and M.Sc (1995) degrees in life sciences from University of Hyderabad; and B.Sc in Biology from Silver Jubilee College (APRDC) Kurnool, SK University (1993) from India. He received President’s fellowship (1992), GATE (1996) and CSIR (2007-2000) fellowships from Government of India. He received Mahindra & Mahindra Educational Award (2000) and Young Clinical Scientist Awards from Flight Attendant Medical Research Institute (FAMRI) in 2007 and 2010. He also received BioBio Young Scientist Award from OMICS publishing group; Michael A. O’Connor Young Investigator Award; RO1 grant Award from NIH/NCI and Research Scholar Grant Award from ACS (2010). He is serving as AIBS/NIH-RO1 Grant reviewer for DT study section. He has published more than 35 research articles in several top journals including Science, Cancer Cell, JCI, Blood, PNAS, Gastroenterology, Cancer Research, JBC, IOVS etc. He is serving as an Executive Editor, Editor and Editorial board member of reputed journals and is serving as a reviewer for 20 scientifi c journals including JCI, Blood, Circulation, Circulation Research, Cancer research, Clinical Cancer research etc. He was honored by giving a position as Keynote Speaker, Chairman, Co-chairman and organizing committee member for several international conferences including Bio- Bio-2009; Bio-Bio-2010; Anal-Bio-2010; Biomarkers & Clinical Research-2010; Diabetes & metabolism-2010; Clinical Research-2011 etc.