Radiolabeled Nanoparticles for Cancer Diagnosis
D. Sakthi Kumar, Aswathy Ravindran Girija in Bionanotechnology in Cancer, 2023
Angiogenesis, the formation of new blood vessels can be studied with RNPs. Integrins are expressed on tumor cells as well as actively proliferating endothelial cells that promote tumor cell invasion, angiogenesis that resulting in metastasis [68–72]. Radiolabeled tracers such as 18F-galacto-RGD, 111In-RP747, and 99mTc-NC100692 for SPECT imaging have been reported for detecting αvβ3 integrin expression related to angiogenesis in tumor [73–76]. Integrin αvβ3-targeted 111In-labeled perfluoro-carbon (PFC) NPs were used to detect angiogenesis in tumor tissue in New Zealand white rabbits bearing tumors and at 18 h after injection, and it was observed the mean tumor radioactivity of integrin αvβ3-targeted PFC NP was four-times than those with non-targeted group (control group) [77].
Mechanotransduction Mechanisms of Hypertrophy and Performance with Resistance Exercise
Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse in The Routledge Handbook on Biochemistry of Exercise, 2020
The family of integrin proteins, 24 in all, are heterodimeric consisting of 18 α and 8 β subunits (13). As transmembrane proteins, the integrin physically connects the extracellular matrix to the intracellular space. Within the cell, the integrin indirectly connects to the actin cytoskeleton through scaffolding proteins positioned at the integrin's cytoplasmic tail such as talin, kindlin, and paxillin. Thus, through its transmembrane nature, the integrin allows communication in a bidirectional manner—both in an inside-out and outside-in fashion (96). Interestingly, research has shed light upon the extended physical continuity from the cytoskeleton into the nucleus, made possible by the linker of the nucleoskeleton and cytoskeleton (LINC) complex (109). This continuous physical link from the extracellular space, through the integrin to the cytoskeleton, and into the nucleus via the LINC complex, directly influences gene expression in a matter of seconds upon mechanical activity, such as muscle tension produced with exercise.
Lymphocyte trafficking from inductive sites to effector sites
Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald in Principles of Mucosal Immunology, 2020
The subsequent strong adhesion of immune cells to vascular endothelial cells is mediated by integrins and their interaction with ligands of the immunoglobulin gene superfamily. Integrins control a wide array of cellular functions, including cell growth, migration, apoptosis, and differentiation. They are heterodimers comprising one α-chain and one β-chain. Both chains exist in multiple forms that, through dimerization, give rise to more than 20 distinct integrin-family members. All major integrins involved in immune-cell migration contain the β1, β2, or β7 integrin chain and are expressed on immune cells, whereas their respective ligands are expressed on the vascular endothelium. Well-known integrin ligands include intercellular adhesion molecules-1 and -2 (ICAM-1, ICAM-2), vascular cell adhesion molecule-1 (VCAM-1), and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) (see Figure 16.2).
Ultrasound-sensitive cRGD-modified liposomes as a novel drug delivery system
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2022
Nour M. AlSawaftah, Vinod Paul, Doua Kosaji, Leen Khabbaz, Nahid S. Awad, Ghaleb A. Husseini
Currently, a class of proteins referred to as the integrin family is being intensively researched for targeted therapy. Integrins are heterodimeric transmembrane glycoproteins comprised of an α and a β subunit. There are 24 known integrin heterodimers made up of 18 α and 8 β subunits [15]. Integrins play a vital role in cell adhesion, motility, signalling, and survival because they bind to various components of the extracellular matrix (ECM) [15,16]. As far as cancer is concerned, integrins were found to play important roles in cancer progression, neoangiogenesis, and some subtypes have been described to be upregulated on many cancer cells, namely αvβ3, αvβ5, and α5β1 [15,17]. The overexpression of certain integrins on cancer cells can be attributed to the need to meet the elevated demand for nutrients and oxygen needed to maintain the rapid growth of tumours.
Emerging therapeutic targets for idiopathic pulmonary fibrosis: preclinical progress and therapeutic implications
Published in Expert Opinion on Therapeutic Targets, 2021
Toyoshi Yanagihara, Ciaran Scallan, Kjetil Ask, Martin R. J. Kolb
Integrins are transmembrane receptors that modify cell adhesion to the ECM and adjacent cells and also interact with the cell cytoskeleton to activate intracellular signaling [45]. Integrins are heterodimers of α and β subunits, assembled from 18 α subunits and 8 β subunits. TGF-β is initially secreted as precursor protein in a latent form coupled with latency-associated protein (LAP), which maintains TGF-β in its inactive form and preventing its interaction with a receptor. A subset of the integrin family (αⅴβ1, αⅴβ5, αⅴβ6, αⅴβ8) binds to LAP to activate TGFβ and plays a key role in tissue fibrosis [45–48]. Especially in the lungs, integrin αⅴβ6 is strongly expressed in AECs in the fibrotic lung from patients with IPF [49], and integrin αⅴβ1 is expressed on lung fibroblasts [46].
Shedding light on developmental drugs for idiopathic pulmonary fibrosis
Published in Expert Opinion on Investigational Drugs, 2020
Paolo Spagnolo, Francesco Bonella, Christopher J Ryerson, Argyris Tzouvelekis, Toby M Maher
Integrins are transmembrane proteins that mediate cell attachment and migration by connecting the actin cytoskeleton to the extracellular matrix. Integrins also participate in more complex cellular events, including survival, proliferation, and regulation of gene expression [37]. The integrin αvβ6, an epithelial restricted molecule, is a major activator of latent TGF-β, and mice lacking the β6 subunit are protected from bleomycin-induced and radiation-induced pulmonary fibrosis [38,39]. In addition, αvβ6 is upregulated in the overlaying epithelial areas of fibrosis in patients with IPF [40]. A phase IIb study evaluating the safety and tolerability of subcutaneously-administered, multiple escalating doses of STX-100/BG00011, a humanized monoclonal antibody directed against αvβ6, in patients with IPF has been terminated early due to safety concerns (NCT03573505; full results pending). Two studies are currently evaluating the safety and tolerability of the αvβ1, β3, and β6 selective inhibitor IDL-2965 in healthy subjects and individuals with IPF (ClinicalTrial.gov Identifier: NCT03949530), and the αvβ6 receptor occupancy (as assessed by PET) by the αvβ1 and β6 selective inhibitor PLN-74809 in patients with IPF (ClinicalTrial.gov Identifier: NCT04072315) (Table 1).
Related Knowledge Centers
- Cadherin
- Coagulation
- Cytoskeleton
- Signal Transduction
- Platelet
- Extracellular Matrix
- Cell Surface Receptor
- Cell Cycle
- Integrin-Like Receptors
- Immunoglobulin Superfamily