Abstract
Simple SummaryTumors are not only composed of cancer cells but also of various infiltrating cells constituting the tumor microenvironment (TME); all these cells produce growth factors which contribute to tumor progression and invasiveness. Among them, transforming growth factor-β1 (TGF-β1) has been shown to be a potent immunosuppressive cytokine favoring cell proliferation and invasion and to be associated with resistance to anticancer treatments. Glycoprotein-A repetition predominant (GARP) plays a critical role in the activation of TGF-β1 and has been shown to be expressed at the membrane of cancer cells and also of regulatory T cells and platelets in the TME. An increased GARP expression has been shown in a variety of cancers. The objective of this review is to highlight GARP’s expression and function in cancer and to evaluate its potential as a predictive and therapeutic follow-up biomarker that could be assessed, in real time, by molecular imaging.Glycoprotein-A repetitions predominant (GARP) is the docking receptor for latent transforming growth factor (LTGF-β) and promotes its activation. In cancer, increased GARP expression has been found in many types of cancer. GARP is expressed by regulatory T cells and platelets in the tumor microenvironment (TME) and can be also expressed by tumor cells themselves. Thus, GARP can be widely present in tumors in which it plays a major role in the production of active TGF-β, contributing to immune evasion and cancer progression via the GARP-TGF-β pathway. The objective of this review is to highlight GARP expression and function in cancer and to evaluate the potential of membrane GARP as a predictive and therapeutic follow-up biomarker that could be assessed, in real time, by molecular imaging. Moreover, as GARP can be secreted, a focus will also be made on soluble GARP as a circulating biomarker.
Highlights
TGF-β, in particular the predominant isoform, TGF-β1, plays a major role in tumor progression due to its pleiotropic effects [1]
Glycoprotein-A repetition predominant (GARP) is considered the membrane docking receptor of latent-TGF-β (LTGF-β) [7,8] and it plays a critical role in the activation of TGF-β, as it allows the interaction of LTGF-β with integrins αvβ6 or αvβ8, a prerequisite step for the release of biologically active TGF-β [9,10]
Glycoprotein-A repetitions predominant (GARP) can be widely present in a tumor, both in tumor cells and in cells of the tumor microenvironment (TME), where it plays a major role in the production of active TGF-β
Summary
TGF-β, in particular the predominant isoform, TGF-β1, plays a major role in tumor progression due to its pleiotropic effects [1]. The GARP gene has been detected in different cell types, such as Tregs and activated B lymphocytes, megakaryocytes and platelets, mesenchymal stromal cells (MSC), hepatic stellate cells and human umbilical vein endothelial cells [13,15]. The GARP gene is detected in many cell types, the expression of the GARP protein has been reported only at the membrane of Tregs [8,30], activated B cells [12], platelets [13,14,30], MSC [15] and hepatic stellate cells [16]. An amplification of GARP gene, as well as GARP expression, has been found in tumor cells, in invasive, metastatic or treatment-resistant tumors [33,34,35]. Single nucleotide polymorphisms (SNP) located in the noncoding regions of human GARP are associated with poor survival in patients with ovarian cancer [36]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
