Integrins: roles in cancer development and as treatment targets

Abstract

The integrin family of cell adhesion proteins promotes the attachment and migration of cells on the surrounding extracellular matrix (ECM). Through signals transduced upon integrin ligation by ECM proteins or immunoglobulin superfamily molecules, this family of proteins plays key roles in regulating tumour growth and metastasis as well as tumour angiogenesis. Several integrins play key roles in promoting tumour angiogenesis and tumour metastasis. Antagonists of several integrins (a5b1, avb3 and avb5) are now under evaluation in clinical trials to determine their potential as therapeutics for cancer and other diseases.

Role of Helicobacter pylori infection in cancer‐associated fibroblast‐induced epithelial‐mesenchymal transition in vitro

“…That is why we have decided to analyze the expression of β1‐integrin mRNA, which as shown in our present work, has also increased. During cancer differentiation and metastasis processes, upregulation of integrins has been linked to cancer invasiveness 79, 80. Among others, the β1‐integrin subunit is expressed in metastatic cells and can be considered as indicator for metastasis 81.…”

Integrins as therapeutic targets: lessons and opportunities

“…During carcinogenesis, the growth of the tumour and its subsequent metastasis is highly dependent on tumour cells being able to regulate their attachment to the extracellular matrix and adjacent cells. Given that integrins play important roles in cell attachment, survival, migration, invasion and angiogenesis 17,[51][52][53] , which are all critical for carcinogenesis, they have attracted considerable attention as potential anticancer targets. Usually anti-integrins are used in combination with other anti-cancer agents but they also have potential as imaging agents in cancer diagnosis [54][55] .…”

Current Molecular Imaging Positron Emitting Radiotracers in Oncology

“…Various radiotracers targeting these biomarkers have been reported [60]. Integrin Targeted Imaging Agents Arginine-glycine-aspartic acid (RGD)-containing components of the interstitial matrix, such as vitronectin, fibronectin, and thrombospondin, bind to the α v β 3 integrin, which is expressed in a number of tumor types, such as melanoma, glioblastoma, ovarian, breast, and prostate cancer [61], and is the most intensively studied integrin due to its critical role in tumor invasion and metastasis. Based on these findings, linear as well as cyclic RGD peptides have been introduced and shown high affinity and excellent selectivity for α v β 3 .…”