The Promise of Integrins as Effective Targets for Anticancer Agents

Rust, William L.; Carper, Stephen W.; Plopper, George E.

doi:10.1155/s1110724302204015

Cited by 28 publications

(21 citation statements)

References 46 publications

(62 reference statements)

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“…A possible approach to controlling the physicochemical properties of the cell environment in 3D in vitro cell migration assays is to use synthetic biomimetic ECM analogs that enable different parameters (such as the microstructure and the availability and the identity of adhesive and proteolytically degradable sequences) to be controlled. While this approach has been investigated essentially in the field of tissue repair and replacement, 142,[144][145][146][147][148][149][150][151][152][153][154][155][156] it could also be used to examine systematically the effects of matrix properties on cell migration. 143,147 The control of the matrix gel properties has become indispensable to the standardization of 3D cell migration assays and, consequently, to the development of anti-migratory therapies against cancer.…”

Section: Discussion Of 3d In Vitro Modelsmentioning

confidence: 99%

“…Most of their migratory-inhibiting effects are based on interference with tumor adhesion to ECM components 53,[155][156][157] or the reduction of tumor cellassociated protease activity 158,159 as shown in Table III, which lists a series of anti-migratory compounds that have reached the clinical trial stage. Table III also lists the types of in vitro cell migration test that have been used to confirm the anti-migratory abilities of these compounds in vitro before they entered the clinical trial phase.…”

Section: W H a T A R E T H E A N T I -M I G R A T O R Y T H E R A Pmentioning

confidence: 99%

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Can anti‐migratory drugs be screened in vitro? A review of 2D and 3D assays for the quantitative analysis of cell migration

Decaestecker

Debeir

Ham

et al. 2006

Medicinal Research Reviews

150

127

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The aim of the present review is to detail and analyze the pros and cons of in vitro tests available to quantify the anti-migratory effects of anti-cancer drugs for their eventual use in combating the dispersal of tumor cells, a clinical need which currently remains unsatisfied. We therefore briefly sum up why anti-migratory drugs constitute a promising approach in oncology while at the same time emphasizing that migrating cancer cells are resistant to apoptosis. To analyze the pros and cons of the various in vitro tests under review we also briefly sum up the molecular and cellular stages of cancer cell migration, an approach that enables us to argue both that no single in vitro test is sufficient to characterize the anti-migratory potential of a drug and that standardization is needed for the efficient quantitative analysis of cell locomotion in a 3D environment. Before concluding our review we devote the final two parts (i) to the description of new prototypes which, in the near future, could enter the screening process with a view to identifying novel anti-migratory compounds, and (ii) to the anti-migratory compounds currently developed against cancer, with particular emphasis on how these compounds were selected before entering the clinical trial phase.

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Section: Discussion Of 3d In Vitro Modelsmentioning

confidence: 99%

Section: W H a T A R E T H E A N T I -M I G R A T O R Y T H E R A Pmentioning

confidence: 99%

Can anti‐migratory drugs be screened in vitro? A review of 2D and 3D assays for the quantitative analysis of cell migration

Decaestecker

Debeir

Ham

et al. 2006

Medicinal Research Reviews

150

127

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“…Trop. Dis., 2005, 11, 3, p. 219 initiate Ras/Erk/MAP kinase pathway, and, consequently, cell proliferation in normal and pathological states (17,82,83,87). FAK is also implicated in controlling cell cycle progression via Jun NH2-terminal kinase (JNK) and preventing apoptosis through a pathway involving the proteins kinase C, phospholipase A2, and p53 (5, 76).…”

Section: Integrinsmentioning

confidence: 99%

“…These include arteriosclerosis, scar keloids, psoriasis, endometriosis, obesity, rheumatoid arthritis, inflammatory and infectious processes, diabetes, retinopathy, tumor growth, and metastasis, among others (16,37). Thus, the inhibition of angiogenesis was adopted as a therapeutic strategy for the treatment of cancer and other diseases, in which neovascularization is one of the pathological components (14,38,87). As recently reviewed (15), more than 60 angiogenesis inhibitors are being evaluated for their anticancer effects in human patients.…”

Section: G Rádis-baptista Integrins Cancer and Snake Toxins (Mini-rmentioning

confidence: 99%

Integrins, cancer and snake toxins (mini-review)

Rádis‐Baptista¹

2005

J. Venom. Anim. Toxins incl. Trop. Dis

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KEY WORDS: integrin, angiogenesis, cancer, apoptosis, snake toxin, snake venom C-type lectin, metalloprotease, disintegrin. CORRESPONDENCE TO:G. RÁDIS-BAPTISTA, Department of Biochemistry and Molecular Biology, Federal University of Ceará, Picí Campus, P.O. Box 6020, 60451-970, Fortaleza, Ceará, Brazil. Phone: +55 85 288 9817. Fax: +55 85 288 9789. Email: radisbra@ufc.br G. Rádis-Baptista INTEGRINS, CANCER AND SNAKE TOXINS (MINI-REVIEW). J. Venom. Anim. Toxins incl. Trop. Dis., 2005, 11, 3, p. 218 INTEGRINSIntegrins constitute a large family of focal adhesion proteins, in other words, transmembrane proteins of adhesion that keep cells attached to the extracellular matrix; the latter composed of an intricate network of proteins and polysaccharides on the cell surface (41). Integrins work as receptors for several types of cell matrix proteins, for example collagen, fibronectin, lamin, vitronectin, and fibrinogen (50).The integrins family comprises, in mammals, at least 24 members of heterodimeric transmembrane proteins, which are formed by the noncovalent association of two glycoproteins: one α subunit out of 19 and one β subunit from 9 types. The diversity of the integrins family is further increased not only by alternative mRNA splicing of some α and β subunits, but also by their post-translational modification (49,110). As example of integrin assembly, β 1 subunit associates with twelve subtypes of the α subunit. Thus, α1β1, α2β1, α3β1, α4β1, α5β1, α6β1, α7β1, α8β1, α9β1, α10β1, α11β1, and αvβ1 are found on almost all the vertebrate cells. In contrast, αv subunit, where v stands for vitronectin receptor, associates with more than one β subunit, making up αvβ1, αvβ3, αvβ5, αvβ6, and αvβ8. Multiple integrins recognize several cell matrix proteins, many of which usually contain the consensus motif of arginineglycine-aspartic acid (RGD). Extracellular divalent cations, such as Ca 2+ and Mg 2+ , influence the specificity and affinity of integrins binding to their ligands (8,102) In addition to participating in the cell matrix attachment, clustering of integrin at the sites of cell contact can activate intracellular signaling through focal adhesion kinase (FAK or pp125 FAK ) and via other associated proteins (18,97). FAK also associates with a number of other adapter, signaling, and cytoskeletal proteins, such as paxillin, Graf (GTPase regulator associated with FAK), cytohesin-1, Grb2, p130 CAS , α-actinin, filamin, and talin (17,92,97 On the other hand, Grb2 directly binding to FAK, in response to integrin activation, G. Rádis-Baptista INTEGRINS, CANCER AND SNAKE TOXINS (MINI-REVIEW). J. Venom. Anim. Toxins incl. Trop. Dis., 2005, 11, 3, p. 219 initiate Ras/Erk/MAP kinase pathway, and, consequently, cell proliferation in normal and pathological states (17,82,83,87). FAK is also implicated in controlling cell cycle progression via Jun NH2-terminal kinase (JNK) and preventing apoptosis through a pathway involving the proteins kinase C, phospholipase A2, and p53 (5, 76).Thus, the "outside-in" signaling medi...

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“…Integrins engage in dialogue with the extracellular matrix, and cadherins mediate cell-cell interactions: these and associated proteins are important in processes ranging from angiogenesis through metastasis to wound healing (Hajra and Fearon 2002;Rust et al 2002). There are many transmembrane receptor proteins that play critical roles in cellular proliferation control, that are fundamental elements of disease-dependent autocrine loops (Zwick et al 2002).…”

Section: Extracellular Versus Intracellular Interactionsmentioning

confidence: 99%