Effect of single-chain antibody targeting of the ligand-binding domain in the anaplastic lymphoma kinase receptor

Stylianou, Dora C.; Maur, Adrian Auf der; Kodack, David P.; Henke, Ralf T.; Hohn, S.; Toretsky, Jeffrey A.; Riegel, Anna T.; Wellstein, Anton

doi:10.1038/onc.2009.184

Cited by 40 publications

(42 citation statements)

References 62 publications

(86 reference statements)

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“…In agreement to our results, ALK mRNA and protein was reportedly expressed at higher levels in 34 gliomas (including low-grade astrocytomas, oligodendrogliomas and GBM) in comparison with adjacent normal brain tissue using in situ hybridisation and immunohistochemistry, respectively 11. Stylianou et al 23 reported elevated ALK and PTN mRNA levels in archival malignant brain tumours (five out of seven GBM, 71.42%). They have also shown inhibition of endothelial invasion in U87MG GBM cell lines using anti-ALK single-chain variable fragment antibodies.…”

Section: Discussionsupporting

confidence: 92%

Anaplastic lymphoma kinase expression and gene alterations in glioblastoma: correlations with clinical outcome

et al. 2016

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Section: Discussionsupporting

confidence: 92%

Anaplastic lymphoma kinase expression and gene alterations in glioblastoma: correlations with clinical outcome

et al. 2016

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“…However, there are four polymorphisms located within 10 kb of the 5′-flanking region and two within 10 kb of the 3′-flanking region, in addition to ∼300 polymorphisms residing in the large intron 2 of the Alk gene, that distinguish the B6 and C3H alleles (http://www.informatics.jax.org/strains_SNPs.shtml), and one or more of these polymorphisms may account for the observed differences in allelic expression. Our results associating Alk with invasion are also congruent with a previous study demonstrating that single-chain variable fragment antibodies targeting Alk can reduce tumor cell invasion in an in vitro setting (29). Additionally, pharmacological inhibition of Alk hindered tumor formation in RT2 mice, in accordance with earlier studies examining the oncogenic properties of Alk (20,25,26,30).…”

Section: Discussionsupporting

confidence: 92%

“…Given the neuroendocrine nature of the tumor type subject to the invasion modifier reported herein, we wonder whether similar tumor types such as small-cell lung cancer or brain cancers might also be affected by this genetic modifier. Interestingly, Alk has been implicated in glioblastoma (29), and as such, this tumor type could be subject to this polymorphic modifier.…”

Section: Discussionmentioning

confidence: 99%

Polymorphic genetic control of tumor invasion in a mouse model of pancreatic neuroendocrine carcinogenesis

Chun

Mao

Chiu

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Cancer is a disease subject to both genetic and environmental influences. In this study, we used the RIP1-Tag2 (RT2) mouse model of islet cell carcinogenesis to identify a genetic locus that influences tumor progression to an invasive growth state. RT2 mice inbred into the C57BL/6 (B6) background develop both noninvasive pancreatic neuroendocrine tumors (PNET) and invasive carcinomas with varying degrees of aggressiveness. In contrast, RT2 mice inbred into the C3HeB/Fe (C3H) background are comparatively resistant to the development of invasive tumors, as are RT2 C3HB6(F1) hybrid mice. Using linkage analysis, we identified a 13-Mb locus on mouse chromosome 17 with significant linkage to the development of highly invasive PNETs. A gene residing in this locus, the anaplastic lymphoma kinase (Alk), was expressed at significantly lower levels in PNETs from invasion-resistant C3H mice compared with invasion-susceptible B6 mice, and pharmacological inhibition of Alk led to reduced tumor invasiveness in RT2 B6 mice. Collectively, our results demonstrate that tumor invasion is subject to polymorphic genetic control and identify Alk as a genetic modifier of invasive tumor growth.anaplastic lymphoma kinase | cancer modifier genes | malignant progression | pancreas cancer | transgenic mouse C ancer is a complex disease governed by environmental and genetic factors, including genetic mutations and polymorphisms that modulate cancer susceptibility (1). Although many investigations have focused on identifying factors that affect initial tumor development (2, 3), data from both human and mouse studies have demonstrated that genetic polymorphisms can modulate multiple aspects of tumorigenesis, such as tumor progression (4-6) and response to therapy (7).In this study, we investigated the effects of genetic background on tumor progression to an invasive growth state, motivated by a provocative observation that mice carrying the same oncogenic transgene but differing in genetic background developed tumors that were markedly distinctive in their invasiveness. This model, the RIP1-Tag2 (RT2) mouse model of islet cell carcinogenesis, develops multiple pancreatic neuroendocrine tumors (PNET) in a relatively synchronous and predictable multistage progression pattern by 12-14 wk of age owing to the expression of the SV40 T antigen oncoprotein (Tag) in the pancreatic β cells (8). The tumorigenesis pathway has predominantly been studied in RT2 mice inbred into the C57BL/6 (B6) background, and the PNETs that arise in this genetic context display a spectrum of invasive phenotypes and can be classified as noninvasive islet tumors (IT), focally invasive type-1 carcinomas (IC1), and broadly invasive type-2 carcinomas (IC2) (9). Surprisingly, we observed that when RT2 mice were inbred into a second strain, C3HeB/Fe (C3H), the tumors that arose were predominantly noninvasive, despite being otherwise similar in their tumorigenesis phenotype. The implication that the invasive phenotype was influenced by genetic background prompted our investigation...

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“…38,39 Here, MPFs were plated into wells of an xCelligence E-culture plate array (Roche, Indianapolis, IN) and followed until they reached confluence and steady-state impedance. Monolayers were then disrupted by scratching with a sterile pipette tip.…”

Section: Electric Impedance Sensingmentioning

confidence: 99%

Impact of Fibroblast Growth Factor-Binding Protein–1 Expression on Angiogenesis and Wound Healing

Tassi

McDonnell

Gibby

et al. 2011

The American Journal of Pathology

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Fibroblast growth factors (FGFs) participate in embryonic development, in maintenance of tissue homeostasis in the adult, and in various diseases. FGF-binding proteins (FGFBP) are secreted proteins that chaperone FGFs stored in the extracellular matrix to their receptor, and can thus modulate FGF signaling. FGFBP1 (alias BP1, FGF-BP1, or HBp17) expression is required for embryonic survival, can modulate FGF-dependent vascular permeability in embryos, and is an angiogenic switch in human cancers. To determine the function of BP1 in vivo, we generated tetracycline-regulated conditional BP1 transgenic mice. BP1-expressing adult mice are viable, fertile, and phenotypically indistinguishable from their littermates. Induction of BP1 expression increased mouse primary fibroblast motility in vitro, increased angiogenic sprouting into subcutaneous matrigel plugs in animals and accelerated the healing of excisional skin wounds. FGF-receptor kinase inhibitors blocked these effects. Healing skin wounds showed increased macrophage invasion as well as cell proliferation after BP1 expression. Also, BP1 expression increased angiogenesis during the healing of skin wounds as well as after ischemic injury to hindlimb skeletal muscles. We conclude that BP1 can enhance FGF effects that are required for the healing and repair of injured tissues in adult animals. The family of fibroblast growth factors (FGFs) encompasses 18 distinct FGF receptor ligands, with a wide expression range and a significant role in angiogenesis, tumor progression, wound healing, and embryonic development.1-4 Many members of the FGF family, such as FGF1 and FGF2, are immobilized in the extracellular matrix (ECM) bound to heparan sulfate proteoglycans (HSPGs) and released from this storage site by proteases and heparanases. 4 -6 The involvement of carrier proteins that shuttle FGFs from their storage site to their receptors represents an alternative mode of regulation of FGF release from the ECM. 1,7 FGF-binding protein 1 (BP1, FGFBP1, FGF-BP1, or HBp17), 8 the best characterized of the three known secreted FGFBPs, 9 is an extracellular chaperone that binds FGF1, 2, 7, 10, and 22 in a reversible, noncovalent manner. 8,10 -12 Binding of the C-terminus of the BP1 protein is sufficient for its interaction with FGF2.13 After binding to BP1, the biochemical and biological activities of FGF are positively modulated.14 Several findings from different laboratories indicate that BP1 can contribute to embryonic development, 15 angiogenesis, tumor growth, and malignant progression, 11,12,14 -20 as well as the maintenance and reinnervation of the neuromuscular junction. 21 We reported earlier that expression of BP1 in SW13 cells induces FGF2 release from the cells, FGF-dependent colony formation in soft agar, and the growth of highly vascularized tumors in nude mice.11 In contrast, depletion of endogenous BP1 from ME180 cells was observed to reduce the release of ECM bound FGF2 into the cell supernatants and to increase FGF2 immobilized on the cell surface.16 Consisten...

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Effect of single-chain antibody targeting of the ligand-binding domain in the anaplastic lymphoma kinase receptor

Cited by 40 publications

References 62 publications

Anaplastic lymphoma kinase expression and gene alterations in glioblastoma: correlations with clinical outcome

Anaplastic lymphoma kinase expression and gene alterations in glioblastoma: correlations with clinical outcome

Polymorphic genetic control of tumor invasion in a mouse model of pancreatic neuroendocrine carcinogenesis

Impact of Fibroblast Growth Factor-Binding Protein–1 Expression on Angiogenesis and Wound Healing

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