ADAM15 Overexpression in NIH3T3 Cells Enhances Cell–Cell Interactions

Herren, Barbara; Garton, Kyle J.; Coats, Scott A.; Bowen‐Pope, Daniel F.; Ross, Russell; Raines, Elaine W.

doi:10.1006/excr.2001.5353

Cited by 62 publications

(55 citation statements)

References 22 publications

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“…Interactions of ADAM-15 disintegrin domain with integrins a v h 3 , a 5 h 1 , and a 9 h 1 have been documented (5)(6)(7), and these may in principle occur either in trans, regulating cell-cell adhesion, or in cis, thereby modulating cell interactions with matrix substrata. Overexpression of ADAM-15 (this is likely the originally described ADAM-15A variant) in NIH 3T3 cells enhanced cell attachment and led to increased cell-cell adhesion, with a concomitant decrease in migration (37). We did not observe increased cell-to-cell interactions in our MDA-MB-435 -transfected clones, but this may depend on the spectrum of adhesive proteins that particular cell types express.…”

Section: Discussionmentioning

confidence: 54%

“…This isoform also decreased cell attachment, which may contribute to the lower Matrigel invasion capabilities of ADAM-15B -expressing cells compared with the ADAM-15A cells. There is substantial evidence that ADAM-15 can influence both cell adhesion and migration (31,36,37). Interactions of ADAM-15 disintegrin domain with integrins a v h 3 , a 5 h 1 , and a 9 h 1 have been documented (5)(6)(7), and these may in principle occur either in trans, regulating cell-cell adhesion, or in cis, thereby modulating cell interactions with matrix substrata.…”

Section: Discussionmentioning

confidence: 99%

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Distinct Functions of Natural ADAM-15 Cytoplasmic Domain Variants in Human Mammary Carcinoma

Zhong

Poghosyan

Pennington

et al. 2008

Molecular Cancer Research

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Adamalysins [a disintegrin and metalloproteinase (ADAM)] are a family of cell surface transmembrane proteins that have broad biological functions encompassing proteolysis, adhesion, and cell signal regulation. We previously showed that the cytoplasmic domain of ADAM-15 interacts with Src family protein tyrosine kinases and the adaptor protein growth factor receptor binding protein 2 (Grb2). In the present study, we have cloned and characterized four alternatively spliced forms of ADAM-15, which differ only in their cytoplasmic domains. We show that the four ADAM-15 variants were differentially expressed in human mammary carcinoma tissues compared with normal breast. The expression of the individual isoforms did not correlate with age, menopausal status, tumor size or grade, nodal status, Nottingham Prognostic Index, or steroid hormone receptor status. However, higher levels of two isoforms (ADAM-15A and ADAM-5B) were associated with poorer relapse-free survival in node-negative patients, whereas elevated ADAM-15C correlated with better relapse-free survival in node-positive, but not in node-negative, patients. The expression of ADAM-15A and ADAM-15B variants in MDA-MB-435 cells had differential effects on cell morphology, with adhesion, migration, and invasion enhanced by expression of ADAM-15A, whereas ADAM-15B led to reduced adhesion. Using glutathione S-transferase pull-down assays, we showed that the cytoplasmic domains of ADAM-15A, ADAM-15B, and ADAM-15C show equivalent abilities to interact with extracellular signal-regulated kinase and the adaptor molecules Grb2 and Tks5/Fish, but associate in an isoform-specific fashion with Nck and the Src and Brk tyrosine kinases. These data indicate that selective expression of ADAM-15 variants in breast cancers could play an important role in determining tumor aggressiveness by interplay with intracellular signaling pathways. (Mol Cancer Res 2008;6(3):383 -94)

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Distinct Functions of Natural ADAM-15 Cytoplasmic Domain Variants in Human Mammary Carcinoma

Zhong

Poghosyan

Pennington

et al. 2008

Molecular Cancer Research

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“…The key molecule in the collective migration was reported to be cadherins, which mediate the cell to cell junction. ADAM15 is known to co-localize with VEcadherin and the over-expression of ADAM15 strengthens cell to cell interaction (Herren et al, 2001). 8F7 inhibited not only invasion and migration but also Science Publications AJI collective cell migration of breast cancer cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Alpha9beta1 integrin also promotes the invasion of breast cancer cells in vitro (Allen et al, 2011) and is expressed by lymphatic and vascular endothelial cells and interacts with VEGF-A, C and D, thereby involved in angiogenesis, lymphangiogensis and metastasis (Vlahakis et al, 2005;. However, it should be pointed out that many reports demonstrated that ADAM15 mediates cell to cell interactions via binding to integrins (Charrier et al, 2007;Eto et al, 2000;Herren et al, 2001), which suggest that tumor cell migration or invasion from primary tumor sites into surrounding tissues might be inhibited by those ADAM15-mediated cell to cell interactions. In sharp contrast, the concept of collective cell migration (invasion of cancer cells as a mass rather than single cell) was introduced for the explanation of tumor invasion and metastasis (Friedl and Gilmour, 2009;Friedl and Wolf, 2008).…”

Section: Ajimentioning

confidence: 99%

The Cell to Cell Interaction of Breast Cancer Cells Regulates Cancer Invasion via Adam15

Ota

Ikesue

Matsui

et al. 2012

American Journal of Immunology

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Increasing evidence suggests that a disintegrin and metalloproteinase 15 (ADAM15) have essential roles in the process of cancer metastasis via degradation of the extracellular matrix and binding to integrins. Among them, ADAM15 possesses an Arg-Gly-Asp (RGD) sequence within its disintegrin domain (d.d., hereafter) and binds to RGD recognizing-integrins such as αvβ3 and α5β1 and also interacts with integrin α9β1 in RGD-independent manner. Although these integrins play important roles in the process of cancer metastasis, the role of the interactions between ADAM15 and integrins during processes of cancer metastasis remains to be elucidated. We produced the specific antibody (8F7) that interferes with the interaction of human ADAM15 and integrin receptors and performed in vitro aggregation assay, invasion assay, proliferation assay, proteinase activity assay and cell-cell adhesion assay. 8F7 inhibited tumor cell aggregation, invasion and migration, but not proliferation of breast cancer cells and proteinase activity of ADAM15. Furthermore, the interactions between ADAM15 and integrin receptors induced collective cell migration, phosphorylation of Akt, which was known to promote invasion of breast cancer cells. These data suggested that the binding of ADAM15 to αvβ3 or α9β1 integrins through its d.d. Induces cell aggregation, migration and invasion of human breast cancer cells with concomitant activation of Akt signaling pathway.

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“…Monolayer Permeability Assay-Horseradish peroxidase flux across A2058 cell monolayers was measured using Transwell cell culture chambers (0.4-m pore polycarbonate filters; Corning) as previously described (26). Briefly, A2058 cells (7.5 ϫ 10 4 ) were cultured for 2-3 days in Transwell units (Corning).…”

Section: Fig 3 Effects Of Anti-tm Antibodiesmentioning

confidence: 99%