Anti‐metastatic and Anti‐invasive Effects of Polymeric Arg‐Gly‐Asp (RGD) Peptide, Poly(RGD), and Its Analogues

Saiki, Ikuo; Murata, Jun; Matsuno, Kōichirō; Ogawa, Ryu; Nishi, Norio; Tokura, Seiichi; Azuma, Ichiro

doi:10.1111/j.1349-7006.1990.tb02624.x

Cited by 41 publications

(17 citation statements)

References 20 publications

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“…Our work complements recent results by Yao and colleagues showing that the inhibition of the a5b1-integrin prevents the extravasation of MDA-MB-231 cells in the lungs of athymic nude mice (37). Similar effects of a5b1-integrin blocking on lung metastasis were shown in other studies for a metastatic rat prostate cancer cell line (38) and a metastatic murine melanoma cell line (39). These and our data point toward an important role of b1-integrin in lung metastasis.…”

Section: Discussionsupporting

confidence: 78%

Norepinephrine Promotes the β1-Integrin–Mediated Adhesion of MDA-MB-231 Cells to Vascular Endothelium by the Induction of a GROα Release

Strell

Niggemann

Voss

et al. 2012

Molecular Cancer Research

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The migratory activity of tumor cells and their ability to extravasate from the blood stream through the vascular endothelium are important steps within the metastasis cascade. We have shown previously that norepinephrine is a potent inducer of the migration of MDA-MB-468 human breast carcinoma cells and therefore investigated herein, whether the interaction of these cells as well as MDA-MB-231 and MDA-MB-435S human breast carcinoma cells with the vascular endothelium is affected by this neurotransmitter as well. By means of a flow-through assay under physiologic flow conditions, we show that norepinephrine induces an increase of the adhesion of the MDA-MB-231 cells, but not of MDA-MB-468 and MDA-MB-435S cells to human pulmonary microvascular endothelial cells (HMVEC). The adhesion of MDA-MB-231 cells was based on a norepinephrine-mediated release of GROa from HMVECs. GROa caused a b1-integrin-mediated increase of the adhesion of MDA-MB-231 cells. Most interestingly, this effect of norepinephrine, similar to the aforementioned induction of migration in MDA-MB-468 cells, was mediated by b-adrenergic receptors and therefore abrogated by b-blockers. In conclusion, norepinephrine has cell line-specific effects with regard to certain steps of the metastasis cascade, which are conjointly inhibited by clinically established b-blockers. Therefore, these results may deliver a molecular explanation for our recently published retrospective data analysis of patients with breast cancer which shows that b-blockers significantly reduce the development of metastases. Mol Cancer Res; 10(2); 197-207. Ó2011 AACR.

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Section: Discussionsupporting

confidence: 78%

Norepinephrine Promotes the β1-Integrin–Mediated Adhesion of MDA-MB-231 Cells to Vascular Endothelium by the Induction of a GROα Release

Strell

Niggemann

Voss

et al. 2012

Molecular Cancer Research

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“…After subcutaneous administration, it reduces frequency of relapse and disease progression [115]. In the early 90s, Poly(Arg-Gly-Asp) was demonstrated to inhibit lung metastasis and migration of B16-BL6 melanoma in mice [116,117]. VivaGel ® is another example of a polymeric drug under clinical development and it is based on a multivalent lysine-dendrimer.…”

Section: Drug Deliverymentioning

confidence: 99%

Peptide-Based Polymer Therapeutics

2014

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Abstract:Polypeptides are envisaged to achieve a major impact on a number of different relevant areas such as biomedicine and biotechnology. Acquired knowledge and the increasing interest on amino acids, peptides and proteins is establishing a large panel of these biopolymers whose physical, chemical and biological properties are ruled by their controlled sequences and composition. Polymer therapeutics has helped to establish these polypeptide-based constructs as polymeric nanomedicines for different applications, such as disease treatment and diagnostics. Herein, we provide an overview of the advantages of these systems and the main methodologies for their synthesis, highlighting the different polypeptide architectures and the current research towards clinical applications.

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“…On the other hand, many animal and human tumor cells can activate and aggregate platelets in vitro (34,35). Tumor-induced platelet aggre gation was inhibited by the Arg-Gly-Asp (RGD)-contain ing peptides derived from the cell-binding domain of fibronectin, thus indicating that the RGD sequence com petitively blocks any interaction between tumor cells, tumor-stimulated platelets (presumably through the Ilb/IIla integrin on the surface) and such adhesive pro teins like fibrinogen and fibronectin (36)(37)(38).…”

Section: Introductionmentioning

confidence: 99%

“…administrations of poly(RGD) or its analogue, poly (RGDT), before or after surgical excision of the primiary tumor on day 21, resulted in a significant reduction of lung tumor colonies, but did not affect the growth (size) of the primary tumor (Table 3) (37,90,92). Multiple treatment of poly(R,G,D) or RGD tripeptide, however, did not decrease the number of lung tumor colonies.…”

Section: Introductionmentioning

confidence: 99%

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Cell Adhesion Molecules and Cancer Metastasis

Saiki

1997

Japanese Journal of Pharmacology

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The adhesive interaction between tumor cells and host cells or the extracellular matrix plays a crucial role in metastasis formation. Therefore, understanding the mechanism controlling metastasis may assist in the development of antimetastatic therapy. We have used synthetic or recombinant polypeptide analogues containing the Arg-Gly-Asp (RGD) sequence found in the functional domains of fibronectin, such as poly(RGD) or CH-271, to regulate the mechanisms involved in cell adhesion during the metastatic process. Poly(RGD) inhibited experimental lung and liver metastasis effectively when coinjected i.v. with various types of tumors. In a model of spontaneous lung metastasis using the B16-BL6 melanoma, repeated administration of this polypeptide before or after surgical excision of the primary tumor resulted in a sig nificant inhibition of tumor metastasis without affecting the growth of the primary tumor and substantially prolonged the survival time of mice. The mechanism responsible for the inhibition of tumor metastasis by the polypeptides is at least partly associated with the ability to interfere with cellular functions such as adhesiveness, motility and invasiveness in the process of metastasis. Combined treatment of the CH-271 fusion polypeptide and anticancer drugs, i.e., anti-adhesion therapy combined with chemotherapy, caused a marked inhibition of lung and liver metastasis of tumors as compared with either treatment alone or with the control. In contrast, the promotion of tumor cell interaction with immune cells via cell adhesion molecules, which differs from the anti-adhesive mechanism, may lead to the induction of anti-tumor im mune responses and, consequently, to the inhibition of tumor metastasis. The transfection of the gene of the B7-1 adhesion molecule into tumor cells (B16-BL6 or K1735-M2 melanoma) resulted in the remarkable reduction of lung metastasis caused by the i.v. injection into mice. Immunization of B7-transfected tumor was effective as a tumor vaccine for preventing the metastasis of B7 negative original tumor cells. Thus, the regulation of the adhesive interaction with tumor cells may provide a new and promising approach for the control and prevention of cancer metastasis.

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Anti‐metastatic and Anti‐invasive Effects of Polymeric Arg‐Gly‐Asp (RGD) Peptide, Poly(RGD), and Its Analogues

Cited by 41 publications

References 20 publications

Norepinephrine Promotes the β1-Integrin–Mediated Adhesion of MDA-MB-231 Cells to Vascular Endothelium by the Induction of a GROα Release

Norepinephrine Promotes the β1-Integrin–Mediated Adhesion of MDA-MB-231 Cells to Vascular Endothelium by the Induction of a GROα Release

Peptide-Based Polymer Therapeutics

Cell Adhesion Molecules and Cancer Metastasis

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