Exploring the Role of RGD-Recognizing Integrins in Cancer

Abstract

Integrins are key regulators of communication between cells and with their microenvironment. Eight members of the integrin superfamily recognize the tripeptide motif Arg-Gly-Asp (RGD) within extracelluar matrix (ECM) proteins. These integrins constitute an important subfamily and play a major role in cancer progression and metastasis via their tumor biological functions. Such transmembrane adhesion and signaling receptors are thus recognized as promising and well accessible targets for novel diagnostic and therapeutic applications for directly attacking cancer cells and their fatal microenvironment. Recently, specific small peptidic and peptidomimetic ligands as well as antibodies binding to distinct integrin subtypes have been developed and synthesized as new drug candidates for cancer treatment. Understanding the distinct functions and interplay of integrin subtypes is a prerequisite for selective intervention in integrin-mediated diseases. Integrin subtype-specific ligands labelled with radioisotopes or fluorescent molecules allows the characterization of the integrin patterns in vivo and later the medical intervention via subtype specific drugs. The coating of nanoparticles, larger proteins, or encapsulating agents by integrin ligands are being explored to guide cytotoxic reagents directly to the cancer cell surface. These ligands are currently under investigation in clinical studies for their efficacy in interference with tumor cell adhesion, migration/invasion, proliferation, signaling, and survival, opening new treatment approaches in personalized medicine.

Oral aktive Peptide: Gibt es ein Patentrezept?

“…Eine Erhçhung der gesamten Lipophilie erzielte eine hçhere Bindungsaffinitätsowie eine hçhere Bioverfügbarkeit des alll-konfigurierten cyclischen Peptids. [185] Als Konsequenz auf das Einfügen von polaren Aminosäuren geht die intestinale Permeabilitätk omplett verloren, welche aber mithilfe des LPCM-Ansatzes wiederhergestellt werden konnte. [29] Dies erklärt auch das Interesse und die ausgiebige Erforschung der zugrundeliegenden physiochemischen Eigenschaften und Aufnahmemechanismen.…”

Nephronectin mediates p38 MAPK‐induced cell viability via its integrin‐binding enhancer motif

“…The requirement of the NPNT EIE‐enhancer motif in the activation of p38 MAPK is a novel finding, making this a potential drug target in tumors with high NPNT expression. Interestingly, though the RGD motif has shown great promise as a therapeutic target , drugs such as cilengitide have failed in clinical trials due to lack of efficiency . Based on the current findings, we therefore suggest that dual targeting of the RGD and EIE‐enhancer motif could prove to be more efficient for cancers with high NPNT levels.…”

A Low Molecular Weight Protein from the Sea Anemone <em>Anemonia viridis</em> with an Anti Angiogenic Activity

“…The amphoteric characteristic is due to a hydrophobic and a hydrophilic poles made of F16 and R11 for SHPI-1 (Fig 7C), and F16 and R12 for BDS-5 (Fig 7A). A KTI from a tick was able to inhibit Trypsin, Elastase and interfere with blood vessel formation [23]. The RGD motif is recognized by Integrins that are membrane proteins playing a major role in cancer progression and metastasis [24].…”