Integrin α2β1 mediates the anti-angiogenic and anti-tumor activities of angiocidin, a novel tumor-associated protein

Sabherwal, Yamini; Rothman, Vicki L.; Dimitrov, Svetoslav; L’Heureux, Darryl Z.; Marcinkiewicz, Cezary; Sharma, Mahesh; Tuszynski, George P.

doi:10.1016/j.yexcr.2006.04.009

Cited by 28 publications

(47 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to avb3, the collagen receptors a1b1 and a2b1 19 and other b1 integrin receptors 20 have been shown to play important roles in angiogenesis and tumor growth. 21 Integrin receptors play a primary role in the motility of cancer cells. They are involved not only in physically tethering cells to the matrix, but also in transmitting signals in both directions that regulate these processes.…”

Section: Introductionmentioning

confidence: 99%

DNAzymes to mouse β1 integrin mRNA in vivo: targeting the tumor vasculature and retarding cancer growth

et al. 2009

View full text Add to dashboard Cite

Previously, we designed a DNAzyme (b1DE) targeting the human b1 integrin subunit, which efficiently digested the mRNA of the b1 integrin subunit and downregulated b1 integrin expression in endothelial cells. This DNAzyme blocked the adhesion of endothelial cells and abolished their ability to form microcapillary tubes in Matrigel. In our present study, we demonstrate that b1DE effectively inhibited neovascularization in Matrigel plugs (BALB/c mice, n ¼ 20) and solid human carcinoma tumors developed in nude mice (BALB/cA nude (nu-/-)-B6.Cg-Foxn1 nu ) (n ¼ 30) using prostate carcinoma cells PC-3 (n ¼ 15) and colon adenocarcinoma cells CX1.1 (n ¼ 15). When injected intratumorally, it significantly reduced the tumor size and number of microvessels developed by both CX1.1 and PC-3 cells within the 3 weeks of experiment duration. Thus, DNAzymes targeting b1 integrin genes can inhibit multiple key tumorigenic processes in vitro and in vivo and may serve as useful anti-cancer agents.

show abstract

Section: Introductionmentioning

confidence: 99%

DNAzymes to mouse β1 integrin mRNA in vivo: targeting the tumor vasculature and retarding cancer growth

et al. 2009

View full text Add to dashboard Cite

show abstract

“…This particular domain of angiocidin contains the TSP-1 binding site; an angiocidin deletion mutant missing this domain fails to bind matrix proteins and loses its protumor effects. 9,10 system). The cells of origin were from 3 tissues in the same patient: benign fibroblasts from an area of normal tissue stroma (EXOS-N), primary osteosarcoma cells from the primary tumor (EXOS-P), and metastatic osteosarcoma cells from a metastatic lesion in the lung (EXOS-M).…”

Section: Synthesis Of Angiocidin Inhibitory Peptidesmentioning

confidence: 99%

“…15 The 25-mer peptide containing a 20 amino acid sequence from angiocidin mediates an antitumor effect by competitively binding to TSP-1. 10 We measured the inhibitory effects of our peptides on TSP-1-mediated gelatinase expression and sarcoma tumor cell invasion. The CSVTCG and 25-mer angiocidin-inhibitory peptides individually downregulated the TSP-1-induced increase in gelatinase expression by 60% to 75% (P ¼ .0001) (Fig.…”

Section: Angiocidin-inhibitory Peptides Block the Effects Of Tsp-1 Onmentioning

confidence: 99%

“…8,9 Overexpression of angiocidin has been shown in many solid epithelial tumors, and increased levels of angiocidin have been demonstrated in the serum of patients with different epithelial malignancies. 10,11 Preliminary reports have shown low to negligible expression of angiocidin in normal adult tissues, making it an attractive molecular target for tumor-specific therapy. 9,12,13 The protumor effects of angiocidin are the result of highaffinity binding interactions with extracellular matrix proteins including thrombospondin-1 (TSP-1), a matrix protein produced in tumors by activated stromal cells of mesenchymal origin.…”

mentioning

confidence: 99%

“…Preliminary data have demonstrated that these peptides are excellent inhibitors of angiogenesis and tumor cell invasion in vitro. 9,10,14 The first of these peptides, a 6-amino acid residue peptide with the sequence CSVTCG, blocks the binding of angiocidin to TSP-1. The second peptide, a 25-amino acid sequence derived from the TSP-1 binding site within the angiocidin molecule, also competitively inhibits the binding of angiocidin to TSP-1.…”

mentioning

confidence: 99%

See 2 more Smart Citations

The role of angiocidin in sarcomas

Liebig

Wilks

Feig

et al. 2009

Cancer

View full text Add to dashboard Cite

We investigated growth kinetics of microalgae, Chlorella vulgaris, in immobilized arrays of nanoliter‐scale microfluidic drops. These static drop arrays enabled simultaneous monitoring of growth of single as well as multiple cells encapsulated in individual droplets. To monitor the growth, individual drop volumes were kept nearly intact for more than a month by controlling the permeation of water in and out of the microfluidic device. The kinetic growth parameters were quantified by counting the increase in the number of cells in each drop over time. In addition to determining the kinetic parameters, the cell‐size distribution of the microalgae was correlated with different stages of the growth. The single‐cell growth kinetics of C. vulgaris showed significant heterogeneity. The specific growth rate ranged from 0.55 to 1.52 day−1 for different single cells grown in the same microfluidic device. In comparison, the specific growth rate in bulk‐scale experiment was 1.12 day−1. It was found that the average cell size changes significantly at different stages of the cell growth. The mean cell‐size increased from 5.99 ± 1.08 to 7.33 ± 1.3 µm from exponential to stationary growth phase. In particular, when multiple cells are grown in individual drops, we find that in the stationary growth phase, the cell size increases with the age of cell suggesting enhanced accumulation of fatty acids in older cells. Biotechnol. Bioeng. 2012; 109: 2987–2996. © 2012 Wiley Periodicals, Inc.

show abstract

Vascular Integrins: Therapeutic and Imaging Targets of Tumor Angiogenesis

Rüegg¹,

Alghisi²

2009

Angiogenesis Inhibition

View full text Add to dashboard Cite

Cells, including endothelial cells, continuously sense their surrounding environment and rapidly adapt to changes in order to assure tissues and organs homeostasis. The extracellular matrix (ECM) provides a physical scaffold for cell positioning and represents an instructive interface allowing cells to communicate over short distances. Cell surface receptors of the integrin family emerged through evolution as essential mediators and integrators of ECM-dependent communication. In preclinical studies, pharmacological inhibition of vascular integrins suppressed angiogenesis and inhibited tumor progression. alpha(V)beta(3) and alpha(V)beta(5) were the first integrins targeted to suppress tumor angiogenesis. Subsequently, additional integrins, in particular alpha(1)beta(1), alpha(2)beta(1), alpha(5)beta(1), and alpha(6)beta(4), emerged as potential therapeutic targets. Integrin inhibitors are currently tested in clinical trials for their safety and antiangiogenic/antitumor activity. In this chapter, we review the role of integrins in angiogenesis and present recent advances in the use of integrin antagonists as potential therapeutics in cancer and discuss future perspectives.

show abstract

Integrin α2β1 mediates the anti-angiogenic and anti-tumor activities of angiocidin, a novel tumor-associated protein

Cited by 28 publications

References 31 publications

DNAzymes to mouse β1 integrin mRNA in vivo: targeting the tumor vasculature and retarding cancer growth

DNAzymes to mouse β1 integrin mRNA in vivo: targeting the tumor vasculature and retarding cancer growth

The role of angiocidin in sarcomas

Vascular Integrins: Therapeutic and Imaging Targets of Tumor Angiogenesis

Contact Info

Product

Resources

About