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Stenina-Adognravi et al. Vessel Plus 2018;2:30 Vessel Plus
DOI: 10.20517/2574-1209.2018.40

Review Open Access

Thrombospondins and remodeling of the tumor
microenvironment

Olga Stenina-Adognravi, Santoshi Muppala, Jasmine Gajeton
Department of Molecular Cardiology, Cleveland Clinic, Cleveland, 44195, USA.

Correspondence to: Dr. Olga Stenina-Adognravi, Department of Molecular Cardiology, Cleveland Clinic, Cleveland, 44195, USA.
E-mail: stenino@ccf.org

How to cite this article: Stenina-Adognravi O, Muppala S, Gajeton J. Thrombospondins and remodeling of the tumor
microenvironment. Vessel Plus 2018;2:30. http://dx.doi.org/10.20517/2574-1209.2018.40

Received: 30 May 2018 First Decision: 21 Aug 2018 Revised: 5 Sep 2018 Accepted: 11 Sep 2018 Published: 10 Oct 2018
Science Editor: Alexander D. Verin Copy Editor: Cui Yu Production Editor: Zhong-Yu Guo

Abstract
Vascular remodeling defines cancer growth and aggressiveness. Although cancer cells produce pro-angiogenic signals,
the fate of angiogenesis critically depends on the cancer microenvironment. Composition of the extracellular matrix
(ECM) and tumor inflammation determine whether a cancer will remain dormant, will be recognized by the immune
system and eliminated, or whether the tumor will develop and lead to the spread and metastasis of cancer cells.
Thrombospondins (TSPs), a family of ECM proteins that has long been associated with the regulation of angiogenesis
and cancer, regulate multiple physiological processes that determine cancer growth and spreading, from angiogenesis
to inflammation, metabolic changes, and properties of ECM. Here, we sought to review publications that describe
various functions of TSPs that link these proteins to regulation of cancer growth by modulating multiple physiological
and pathological events that prevent or support tumor development. In addition to its direct effects on angiogenesis,
TSPs have important roles in regulation of inflammation, immunity, ECM properties and composition, and glucose and
insulin metabolism. Furthermore, TSPs have distinct roles as regulators of remodeling in tissues and tumors, such that
the pathways activated by a single TSP can interact and influence each other. The complex nature of TSP interactions
and functions, including their different cell- and tissue-specific effects, may lead to confusing results and controversial
conclusions when taken out of the context of interdisciplinary and holistic approaches. However, studies of TSP
functions and roles in different systems of the organism offer an integrative view of tumor remodeling and a potential for
finding therapeutic targets that would modulate multiple complementary processes associated with cancer growth.

Keywords: Thrombospondin, angiogenesis, inflammation, cancer

INTRODUCTION
The studies of cancer initiation and progression have focused on the molecular and cellular signaling

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
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