Laminin-binding integrin alpha 7 beta 1: functional characterization and expression in normal and malignant melanocytes.

Kramer, Randall H.; Vu, Mai; Cheng, Yao-Fen; Ramos, Daniel M.; Timpl, Rupert; Waleh, Nahid

doi:10.1091/mbc.2.10.805

Cited by 126 publications

(60 citation statements)

References 58 publications

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“…The tethering to LM was totally blocked by Ca 2+ depletion, whereas some still tethered at 4°C condition (46% of control). From these data, it is unlikely that other LM binding integrins such as α7β1 (Kramer et al, 1991) play roles in Colo201 tethering, since all the integrin mediated adhesion should be abolished at 4°C. Then, we asked the contribution of a 67 kDa monomeric polypeptide reported as a high affinity laminin receptor (Rao et al, 1983).…”

Section: Discussionmentioning

confidence: 91%

Laminin mediates tethering and spreading of colon cancer cells in physiological shear flow

et al. 1999

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Summary Under the physiological shear condition, cultured colon cancer cells bound to laminin (LM), but not to fibronectin or vitronectin. Most of the tethered cells did not roll, but arrested immediately and spread within 10-30 min on LM under the continuous presence of shear flow. The tethering of Colo201 was partially inhibited by monoclonal antibodies (mAbs) to α6 integrin and a combination of mAbs to β1 and β4 integrins, but not by mAb to 67KD laminin receptor. Some Colo201 cells still tethered at 4°C. This suggests that α6β1 and α6β4 integrins participate in Colo201 tethering on LM, although other non-integrin molecules play roles. In contrast, the spread of Colo201 was effectively inhibited by the mAbs to integrin α2, α6 and β1 chains. The effect of anti-α2 plus anti-α6 mAbs was almost equal to anti-β1, suggesting that Colo201 cells mainly use α2β1 and α6β1 integrins for spreading on LM. When the cells were perfused on subconfluent endothelial cells (HUVEC) cultured on LM, they did not tether on HUVEC but did on coated LM exposed at intercellular gap area. Immunohistochemistry revealed that LM abundantly existed in the cytosol of human portal and hepatic vein endothelial cells. These data suggest that LM can mediate from tethering to spreading of colon cancer cells under the blood flow and plays an essential role in haematogeneous metastasis.

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Section: Discussionmentioning

confidence: 91%

Laminin mediates tethering and spreading of colon cancer cells in physiological shear flow

et al. 1999

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“…Up to now, no adhesionblocking antibodies to ␣7 integrin are available. The best evidence for ␣7␤1 integrin being a laminin receptor is the fact that it binds to laminin in vitro; thus, it has been isolated by affinity chromatography on laminin-1 (11,30). Other lamininbinding integrins or non-integrin laminin receptors seem responsible for the adhesion of 293 and 530 cells to laminin-1.…”

Section: Resultsmentioning

confidence: 99%

Specific Induction of Cell Motility on Laminin by α7 Integrin

Echtermeyer

Schober

Pöschl

et al. 1996

Journal of Biological Chemistry

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Laminin, the major glycoprotein of basement membranes, actively supports cell migration in development, tissue repair, tumor growth, metastasis, and other pathological processes. Previously we have shown that the locomotion of murine skeletal myoblasts is specifically and significantly enhanced on laminin but not on other matrix proteins. One of the major laminin receptors of myoblasts is the ␣7␤1 integrin, which was first described in human MeWo melanoma cells and Rugli glioblastoma cells. In order to investigate and directly test the role of the ␣7 integrin in cell migration on laminin, we expressed the murine ␣7B splice variant in human 293 kidney cells and 530 melanoma cells which cannot migrate on laminin and are devoid of endogenous ␣7. Northern blotting of the transfected cells showed that the ␣7 mRNA was expressed efficiently, and the protein was detected on the cell surface by immunofluorescence and fluorescence-activated cell sorter analysis. Cell motility measurements by computer-assisted time-lapse videomicroscopy of the ␣7-transfected cells revealed an 8 -10-fold increase in motility on laminin-1 and its E8 fragment, but not on fibronectin. Mock-transfected cells did not migrate significantly on laminin or on fibronectin. Similarly, transmigration of ␣7-transfected 293 cells through laminin-coated filters in a Boyden chamber assay was significantly enhanced in comparison to mocktransfected cells. These findings prove that ␣7 integrin expression confers a gain of function-motile phenotype to immobile cells and may be responsible for transduction of the laminin-induced cell motility.Cells utilize extracellular matrix to migrate during embryonic development, tissue regeneration, and invasion of tissues in inflammation and tumor metastasis (reviewed in Ref. 1). Laminin-1, a major glycoprotein of basement membranes, has been shown to promote migration of different cell types including neural crest cells (2), skeletal myoblasts (3), or B16 mouse melanoma cells (4). The mechanism of laminin-induced cell locomotion and the cellular receptors mediating the locomotor signals are, however, not known. Integrin-and non-integrin receptors are involved in the specific adhesion of cells to laminin. Dystroglycan, a 156-kDa protein forms a transmembrane linkage together with other proteins between laminin-2 and dystrophin in the muscle cell membrane (5); a high affinity laminin receptor of 67 kDa has been isolated from several tumor cells, myoblasts, and other primary cells (for reviews, see Refs. 6 -8). Five laminin-binding integrins of the ␤1 family recognize different sites and isoforms of laminin: ␣6␤1 (9, 10) and ␣7␤1 (11, 12) bind to laminin-1, recognizing specifically the E8 domain; ␣1␤1 binds to a cryptic site in the E1 region of laminin (13), but also to types I and IV collagen (14). The ␣3␤1 integrin binds to laminin-5 (kalinin) (15) and to other matrix proteins; ␣2␤1 is predominantly a collagen receptor (16), but when isolated from endothelial cells it also binds to laminin-1 (17).While much has been publi...

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“…The E8-binding site is dependent on the conformation, with a major contribution made by the a1 chain (Deutzmann et al, 1990). Some muscle or melanoma cell lines seem to use the related integrin a7pl instead of a6pl for binding to E8 (von der Mark et al, 1991;Kramer et al, 1991). Further integrins implicated in laminin binding are alpl (Hal1 et al, 1990;Forsberg et al, 1990;Tawil et al, 1990;Rossino et al, 1990;Kramer et al, 1990) and a2pl (Elices and Hemler, 1989;Languino et al, 1989;Kirchhofer et al, 1990), which are also the major receptors for various collagen types (Vandenberg et a]., 1991; Gullberg et al, 1992;Pfaff et al, 1993; Correspondence to R. Timpl, Max-Planck-Institut fur Biochemie, D-82152 Martinsried Abbreviation.…”

mentioning

confidence: 99%

Binding of Purified Collagen Receptors (α1β1, α2β1) and RGD‐Dependent Integrins to Laminins and Laminin Fragments

Pfaff

Göhring

Brown

et al. 1994

European Journal of Biochemistry

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Integrins alp1 and a2/3l, when purified by collagen affinity chromatography, showed distinct binding to mouse tumor laminin-1, which has the chain composition alplyl. The binding was, however, about 10-fold lower than to collagen IV. Only little (alpl) or no binding (a2pl) was observed to two different laminin isoforms (a2ply1, a2p2yl) from human placenta. Binding to laminin-1 was abolished by EDTA and could be specifically inhibited by antibodies to the respective integrin a subunit. These antibodies also inhibited cell adhesion to collagens. The binding of soluble integrins was weaker than that of immobilized integrins but could be enhanced by an activating anti@ integrin). No enhancement was observed for immobilized integrins. Studies with laminin-1 fragments demonstrated lack of binding to the major cell-adhesive fragment E8 from the long arm, fragments E3 and E4, involved in heparin-binding and self-assembly, respectively, and fragment P1, corresponding to the inner segments of the short arms. A larger short-arm fragment (ElXNd), which lacks the N-terminal pl chain domains V and VI, was as active as laminin. Together, these results, suggested the localization of the binding sites for alp1 and a2pl to the N-terminal region of the laminin a1 chain. Fragment P1 but not intact laminin-1 bound to aVp3 integrin in an EDTA-sensitive and RGD-sensitive manner, underscoring previous data on the cryptic nature of the RGD site in laminin-1. Further analyses by surface plasmon resonance assays demonstrated a KD = 50 nM for a2plllaminin-1 bindmg and a KD = 450 nM for aVp3lfragment P1 binding and confirmed the antipl-mediated increase in affinity for a2pl.

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Laminin-binding integrin alpha 7 beta 1: functional characterization and expression in normal and malignant melanocytes.

Cited by 126 publications

References 58 publications

Laminin mediates tethering and spreading of colon cancer cells in physiological shear flow

Laminin mediates tethering and spreading of colon cancer cells in physiological shear flow

Specific Induction of Cell Motility on Laminin by α7 Integrin

Binding of Purified Collagen Receptors (α1β1, α2β1) and RGD‐Dependent Integrins to Laminins and Laminin Fragments

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