Structural Studies on Angiogenin, a Protein Implicated in Neovascularization during Tumour Growth

Acharya, K.R.; Leonidas, D.D.; Papageorgiou, Anastassios C.; Russo, Aniello; Shapiro, Robert

doi:10.1007/978-1-4757-9185-3_19

Cited by 3 publications

(1 citation statement)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, the studies presented herein indicate that the systemic dissemination and establishment of human prostate tumor cells appear to be particularly sensitive to angiogenin antagonization in spite of the redundancy of proangiogenic factors, including basic fibroblast growth factor, vascular endothelial cell growth factor and interleukin-8, 32,33 known to be produced by cells of the PC-3 lineage. Ongoing investigations will further define the use of angiogenin inhibitors, including DNA medicines, 34 chimerized and humanized MAb 26-2F analogues 35 and small molecule drugs, 36 for the prevention and management of metastatic prostate and other cancers.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of prostate carcinoma establishment and metastatic growth in mice by an antiangiogenin monoclonal antibody

Olson

Byers

Key³

et al. 2002

Intl Journal of Cancer

View full text Add to dashboard Cite

A neutralizing monoclonal antibody (MAb) 26-2F to human angiogenin, a potent inducer of neovascularization, has been shown previously to prevent or delay the appearance of angiogenin-secreting human colon, fibrosarcoma and lung tumor cell xenografts implanted subcutaneously (s.c.) into athymic mice. In an analogous model system, we report here that the antibody also prevents the establishment of PC-3 androgen-independent human prostate cancer tumors in, on average, 40% of treated mice (p < 0.0001, survivor analysis). Intriguingly, combining MAb 26-2F together with cisplatin and suramin, 2 therapeutic agents that together showed little antitumor activity in the aforementioned model, resulted in an even greater degree of protection (71% protected, p ‫؍‬ 0.009 compared to antibody treatment alone). This protective effect persisted several weeks after cessation of treatment. Additionally, prophylactic systemic administration of MAb 26-2F dramatically reduced by 50% the formation of spontaneous regional metastasis originating from primary growth in the prostate gland of PC-3M cells, highly metastatic variants of PC-3. Protection from metastasis was still significant when treatment with MAb 26-2F was delayed until after the primary tumor was well established. The antibody is not directly cytotoxic to either cell type, both of which secrete angiogenin in vitro and when growing as tumors in vivo, but changes the pattern of vascularity in primary tumors growing orthotopically. These findings, together with the observation that angiogenin protein and mRNA are apparently overexpressed in cancerous vs. normal human prostate tissues, demonstrate that angiogenin antagonism represents a promising new approach for preventing progression and metastasis of clinical prostate cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of prostate carcinoma establishment and metastatic growth in mice by an antiangiogenin monoclonal antibody

Olson

Byers

Key³

et al. 2002

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

Untitled

Adams

Subramanian

1999

Angiogenesis

View full text Add to dashboard Cite

Angiogenin is a member of the ribonuclease superfamily, which shows an ever expanding collection of molecules being identified and cloned. It was initially isolated from the conditioned medium of cultured tumour cells. Its angiogenic activity appears to be critical for the maintenance and support of tumour growth. Angiogenin also plays a role in a number of non-malignant vasculoproliferative pathological conditions. Along with other related molecules, it has been identified in a wide variety of somatic tissues in adult and embryonic stages of vertebrate development. This suggests that angiogenin and related molecules are likely to play a vital role in normal physiology. Angiogenin is detectable in serum and to date has been implicated as a mitogen for vascular endothelial cells, an immune modulator with suppressive effects on polymorphonuclear leukocytes, an activator of certain protease cascades such as matrix metalloproteases and plasminogen-activated plasmin pathways, as well as an adhesion molecule. However, the role of the angiogenin family in both normal and abnormal physiology and in development will only fully be realised by genetic approaches involving gene deletion.

show abstract

Nucleotide substrate binding characterization in human pancreatic-type ribonucleases

et al. 2019

View full text Add to dashboard Cite

Human genome contains a group of more than a dozen similar genes with diverse biological functions including antiviral, antibacterial and angiogenesis activities. The characterized gene products of this group show significant sequence similarity and a common structural fold associated with binding and cleavage of ribonucleic acid (RNA) substrates. Therefore, these proteins have been categorized as members of human pancreatic-type ribonucleases (hRNases). hRNases differ in cell/tissue localization and display distinct substrate binding preferences and a wide range of ribonucleolytic catalytic efficiencies. Limited information is available about structural and dynamical properties that influence this diversity among these homologous RNases. Here, we use computer simulations to characterize substrate interactions, electrostatics and dynamical properties of hRNases 1–7 associated with binding to two nucleotide substrates (ACAC and AUAU). Results indicate that even with complete conservation of active-site catalytic triad associated with ribonucleolytic activity, these enzymes show significant differences in substrate interactions. Detailed characterization suggests that in addition to binding site electrostatic and van der Waals interactions, dynamics of distal regions may also play a role in binding. Another key insight is that a small difference in temperature of 300 K (used in experimental studies) and 310 K (physiological temperature) shows significant changes in enzyme-substrate interactions.

show abstract

Structural Studies on Angiogenin, a Protein Implicated in Neovascularization during Tumour Growth

Cited by 3 publications

References 36 publications

Inhibition of prostate carcinoma establishment and metastatic growth in mice by an antiangiogenin monoclonal antibody

Inhibition of prostate carcinoma establishment and metastatic growth in mice by an antiangiogenin monoclonal antibody

Untitled

Nucleotide substrate binding characterization in human pancreatic-type ribonucleases

Contact Info

Product

Resources

About