Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/53788
Title: ISTHMIN IS A NOVEL VASCULAR PERMEABILITY INDUCER THAT INFLUENCES METASTASIS AND WOUND HEALING
Authors: SHRUTHI VENUGOPAL
Keywords: Isthmin, Angiogenesis, Cancer, Metastasis,
Issue Date: 24-Jan-2014
Source: SHRUTHI VENUGOPAL (2014-01-24). ISTHMIN IS A NOVEL VASCULAR PERMEABILITY INDUCER THAT INFLUENCES METASTASIS AND WOUND HEALING. ScholarBank@NUS Repository.
Abstract: Isthmin (ISM) is a novel angiogenesis inhibitor which exerts its biological effect by binding avß5 and GRP78 on endothelial cells (ECs). Understanding the full spectrum of ISM¿s endogenous roles is required in order to develop mechanism-based drugs to treat angiogenesis-related disorders. In this work, I discovered that ISM is also a novel vascular permeability inducer, triggering vascular leakage both in vitro and in vivo. Mechanistic investigation revealed that ISM induces vascular permeability via activation of Src-kinase, disruption of EC adherens junctions and induction of apoptosis. I also demonstrated that systemically delivered ISM inhibits pulmonary metastasis, through inhibition of angiogenesis and inducing cell apoptosis. However, an increase in tumor cell homing to the lung was observed when ISM was delivered immediately before tumor cell inoculation, suggesting that ISM-induced vascular permeability facilitates tumor cell extravasation. Furthermore, topical application of recombinant ISM delayed wound healing through inhibition of angiogenesis, accompanied by a reduction in granulation tissue formation and increased macrophage infiltration. These results suggested a potential role of ISM in regulating inflammation. Taken together, this work identified ISM as a novel vascular permeability inducer that may play important roles in tumor metastasis and would healing.
URI: http://scholarbank.nus.edu.sg/handle/10635/53788
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