Blood Platelets Contain and Secrete Laminin-8 (α4β1γ1) and Adhere to Laminin-8 via α6β1 Integrin

Geberhiwot, Tarekegn; Ingerpuu, Sulev; Pedraza, Claudio; Neira, Mauricio; Lehto, Ulla; Virtanen, Ismo; Kortesmaa, Jarkko; Tryggvason, Karl; Engvall, Eva; Patarroyo, Manuel Elkín

doi:10.1006/excr.1999.4653

Cited by 53 publications

(55 citation statements)

References 50 publications

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“…However, the laminin ␣1LG1-3 structure needs to be associated with the adjacent rod domain of the long arm to express strong binding activity for ␣ 6 ␤ 1 integrin (50, 51). Laminin-8 was in fact recently shown to bind cells via the ␣ 6 ␤ 1 integrin (42,52), which could be confirmed in the present study. This interaction was furthermore specifically inhibited by antibodies against ␣4LG1-3 but not by antibodies against ␣4LG4 -5 (Table III).…”

Section: Discussionsupporting

confidence: 88%

“…The principal fragments released showed a limited size heterogeneity and included C-terminal fragments of 43-45 kDa and N-terminal fragments of 180 -210 kDa. The latter correspond to the 180 -200-kDa ␣4 chains previously detected in embryo extracts (5), leiomyosarcoma cells (11), and platelet laminin-8 (52). This indicates at least a partial release of ␣4LG4 -5, which, however, was not identified in the previous studies.…”

Section: Discussionsupporting

confidence: 47%

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Structural and Functional Analysis of the Recombinant G Domain of the Laminin α4 Chain and Its Proteolytic Processing in Tissues

Talts¹,

Sasaki²,

Miosge³

et al. 2000

Journal of Biological Chemistry

128

147

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The C-terminal G domains of laminin ␣ chains have been implicated in various cellular and other interactions. The G domain of the ␣4 chain was now produced in transfected mammalian cells as two tandem arrays of LG modules, ␣4LG1-3 and ␣4LG4 -5. The recombinant fragments were shown to fold into globular structures and could be distinguished by specific antibodies. Both fragments were able to bind to heparin, sulfatides, and the microfibrillar fibulin-1 and fibulin-2. They were, however, poor substrates for cell adhesion and had only a low affinity for the ␣-dystroglycan receptor when compared with the G domains of the laminin ␣1 and ␣2 chains. Yet antibodies to ␣4LG1-3 but not to ␣4LG4 -5 clearly inhibited ␣ 6 ␤ 1 integrin-mediated cell adhesion to laminin-8, indicating the participation of ␣4LG1-3 in a cell-adhesive structure of higher complexity. Proteolytic processing within a link region between the ␣4LG3 and ␣4LG4 modules was shown to occur during recombinant production and in endothelial and Schwann cell culture. Cleavage could be attributed to three different peptide bonds and is accompanied by the release of the ␣4LG4 -5 segment. Immunohistology demonstrated abundant staining of ␣4LG1-3 in vessel walls, adipose, and perineural tissue. No significant staining was found for ␣4LG4 -5, indicating their loss from tissues. Immunogold staining demonstrated an association of the ␣4 chain primarily with microfibrillar regions rather than with basement membranes, while laminin ␣2 chains appear primarily associated with various basement membranes.The protein family of laminins consists of at least 12 different isoforms, which are mainly localized in basement membranes. They are involved in major biological functions such as interactions with cellular receptors and the formation of networks that are intermingled with and bound to networks of collagen type IV (1, 2). Most of these heterotrimeric isoforms consist of ␤1/␤2 and ␥1 chains but differ in their ␣ chains, ␣1 to ␣5. The ␣4 chain (200 kDa) is the shortest variant known so far and is present in laminin-8 (␣4␤1␥1) and laminin-9 (␣4␤2␥1) (3-5). The existence of such relatively small laminins was originally indicated from biosynthetic studies with endothelial and adipose cells (6, 7), but their molecular nature was only understood after the complete human (8, 9) and mouse (4, 10, 11) ␣4 chain sequences became available. The domain structure of the ␣4 chain (1816 residues) predicted a small Nterminal region contributing a truncated short arm structure, a coiled-coil domain II/I used for chain association, and a large C-terminal G domain. This prediction was confirmed by electron microscopy of laminin-8 and -9, which lacked one of the three short arm structures found in other laminins (3, 4).Northern and in situ hybridization demonstrated a moderate to strong expression of the ␣4 chain in heart, lung, skeletal muscle, and skin, while some other tissues were negative (4, 8 -11). The chain was also expressed at midgestation stages of mouse development (4, 11) and in va...

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 47%

Structural and Functional Analysis of the Recombinant G Domain of the Laminin α4 Chain and Its Proteolytic Processing in Tissues

Talts¹,

Sasaki²,

Miosge³

et al. 2000

Journal of Biological Chemistry

128

147

View full text Add to dashboard Cite

show abstract

“…21,22 We have previously shown that mouse multipotent hematopoietic FDCP-mix cells adhere to laminin-10/11, 35 suggesting that these laminins might also interact with hematopoietic progenitors. Recent studies have shown binding of monoblastic, T-, and B-lymphoid cell lines and CD4 ϩ lymphocytes to laminin-8 and laminin-10/11, platelets to laminin-8, and mouse integrin ␤2-deficient granulocytes to laminin-10/11, 41,[52][53][54][55] suggesting specific roles for different laminin isoforms in interactions with lineagedifferentiated and mature hematopoietic cells. However, the cellular interactions of ␣4 and ␣5 laminin isoforms with human hematopoietic stem and progenitor cells have been unclear.…”

Section: Discussionmentioning

confidence: 99%

Laminin isoform–specific promotion of adhesion and migration of human bone marrow progenitor cells

Kortesmaa

Tryggvason

et al. 2003

Blood

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110

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Laminins are ␣␤␥ heterotrimeric extracellular proteins that regulate cellular functions by adhesion to integrin and nonintegrin receptors. Laminins containing ␣4 and ␣5 chains are expressed in bone marrow, but their interactions with hematopoietic progenitors are unknown. We studied human bone marrow cell adhesion to laminin-10/11 (␣5␤1␥1/␣5␤2␥1), laminin-8 (␣4␤1␥1), laminin-1 (␣1␤1␥1), and fibronectin. About 35% to 40% of CD34 ؉ and CD34 ؉ CD38 ؊ stem and progenitor cells adhered to laminin-10/11, and 45% to 50% adhered to fibronectin, whereas they adhered less to laminin-8 and laminin-1. Adhesion of CD34 ؉ CD38 ؊ cells to laminin-10/11 was maximal without integrin activation, whereas adhesion to other proteins was dependent on protein kinase C activation by 12-tetradecanoyl phorbol-13-acetate (TPA). Fluorescence-activated cell-sorting (FACS) analysis showed expression of integrin ␣6 chain on most CD34 ؉ and CD34 ؉ CD38 ؊ cells. Integrin ␣6 and ␤1 chains were involved in binding of both cell fractions to laminin-10/11 and laminin-8. Laminin-10/11 was highly adhesive to lineagecommitted myelomonocytic and erythroid progenitor cells and most lymphoid and myeloid cell lines studied, whereas laminin-8 was less adhesive. In functional assays, both laminin-8 and laminin-10/11 facilitated stromal-derived factor-1␣ (SDF-1␣)-stimulated transmigration of CD34 ؉ cells, by an integrin ␣6 receptor-mediated mechanism. In conclusion, we demonstrate laminin isoform-specific adhesive interactions with human bone marrow stem, progenitor, and more differentiated cells

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“…Laminin is a basement constituent (32) that is degraded during invasive neoplasia preferentially by plasmin and plasma metalloproteinases (33)(34)(35). In addition, laminin has been described as constituent of blood platelets (36). Detectable plasma levels of laminin fragments may potentially indicate basement membrane destruction accompanying invasive disease as described for other laminin fragments detected in urine of cancer patients (37).…”

Section: Discussionmentioning

confidence: 99%

Plasma from Cancer Patients Featuring a Characteristic Protein Composition Mediates Protection against Apoptosis

Vejda

Posovszky

Zelzer

et al. 2002

Molecular & Cellular Proteomics

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By comparative proteome analysis we searched for characteristic alterations of human plasma accompanying neoplastic disease. We identified protein alterations in plasma of prostate-, lung-, and breast-cancer patients in comparison to controls, comprising elevated levels of fibrinogen ␥-chain dimer, degradation products of antiplasmin and laminin ␥-chain, and elevated levels of acute phase proteins. The latter proteins and laminin fragments have been described as anti-apoptotic factors. We raised the question whether these alterations may have any relevance for the regulation of apoptosis. In contrast to plasma derived from healthy donors, samples from prostate-, lung-, and breast-cancer patients selectively inhibited Fas-and staurosporine-induced apoptosis in Jurkat cells but remained ineffective upon UV light-induced apoptosis. These data suggested that inhibition occurred by extracellular interference with apoptosis induction. Supporting this hypothesis, we found that formation of the CD95 death-inducing signal complex was strongly inhibited in the presence of plasma from cancer patients.

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Blood Platelets Contain and Secrete Laminin-8 (α4β1γ1) and Adhere to Laminin-8 via α6β1 Integrin

Cited by 53 publications

References 50 publications

Structural and Functional Analysis of the Recombinant G Domain of the Laminin α4 Chain and Its Proteolytic Processing in Tissues

Structural and Functional Analysis of the Recombinant G Domain of the Laminin α4 Chain and Its Proteolytic Processing in Tissues

Laminin isoform–specific promotion of adhesion and migration of human bone marrow progenitor cells

Plasma from Cancer Patients Featuring a Characteristic Protein Composition Mediates Protection against Apoptosis

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