Tenascin variants: differential binding to fibronectin and distinct distribution in cell cultures and tissues.

Chiquet‐Ehrismann, Ruth; Matsuoka, Yoichiro; Hofer, Urs; Spring, Jürg; Bernasconi, Carlo; Chiquet, Matthias

doi:10.1091/mbc.2.11.927

Cited by 146 publications

(96 citation statements)

References 35 publications

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“…In chick tissues, the intermediate sized and largest isoforms of Tn-C (containing variable numbers or all alternatively spliced domains, respectively) are known to be distributed in smooth muscle and underneath the epithelial lining of the villi, paralleling our immunohistochemical analysis of human tissues. 49 In a previous study on breast cancers using a conventional Tn-C antibody, it was shown that expression at invasion sites correlates with a higher proliferation rate of cancer cells and is a predictor of local recurrence and metastasis. 13,14 We have showed that Tn-C molecules expressed at the invasion fronts of tumors may chiefly be of the large variant type.…”

Section: Discussionmentioning

confidence: 98%

“…The smallest variant (with complete omission of the alternatively spliced region) binds to fibronectin with higher affinity than the large variants and is incorporated into the matrix. 49,50 This difference in binding capability between the Tn-C variants may account for the variation in staining patterns between the two antibodies. In chick tissues, the intermediate sized and largest isoforms of Tn-C (containing variable numbers or all alternatively spliced domains, respectively) are known to be distributed in smooth muscle and underneath the epithelial lining of the villi, paralleling our immunohistochemical analysis of human tissues.…”

Section: Discussionmentioning

confidence: 99%

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Involvement of Large Tenascin-C Splice Variants in Breast Cancer Progression

Tsunoda

Inada

Kalembeyi

et al. 2003

The American Journal of Pathology

104

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Alternative splicing of fibronectin-like type III (FNIII) repeats of tenascin-C (Tn-C) generates a number of splice variants. The distribution of large variants, typical components of provisional extracellular matrices that are up-regulated during tumor stroma remodeling, was here studied by immunoblotting and immunohistochemistry using a monoclonal antibody against the FNIII B domain (named 4C8MS) in a series of human breast cancers. Large Tn-C variants were found at only low levels in normal breast tissues, but were highly expressed at invading sites of intraductal cancers and in the stroma of invasive ductal cancers, especially at invasion fronts. There was a positive correlation between the expression of large Tn-C variants and the cell proliferation rate determined by immunolabeling of the Ki-67 antigen. Of the Tn-C recombinant fragments (all FNIII repeats or mFNIII FL, the conserved FNIII domain only, the epidermal growth factor-like domain, and the fibrinogen-like domain) which were expressed by CHO-K1 cells transfected with mouse Tn-C cDNAs, only the mFNIII FL enhanced in vitro migration and mitotic activity of mammary cancer cells derived from a Tn-C-null mouse. Addition of 4C8MS blocked the function of mFNIII FL. These findings provide strong evidence that the FNIII alternatively spliced region has important roles in tumor progression of breast cancer. During tumor progression, the cancer stroma becomes remodeled by both tumor cells and stromal cells, and protein components of the extracellular matrix (ECM) are dynamically changed by degradation and neosynthesis. Cellular interaction with the ECM strongly influences the behavior of cancer and stromal cells, resulting in modulation of cell growth, migration, differentiation, and apoptosis. 1-3 Compositional change of the ECM in cancer stroma is thus a key determinant of tumor growth and cancer progression. A variety of ECM glycoproteins, such as tenascin-C (Tn-C) and fibronectin, are overexpressed in cancer stroma. In addition, splice variants of these proteins, which are generally absent in normal adult tissues, become predominant. 4 -11 It has been reported that overexpression of Tn-C in breast cancer is related to a poor prognosis, and local and distant recurrence, 12-14 this being attributable to the ability to promote cell migration and proliferation demonstrated in vitro. 15,16 Tn-C is a hexameric glycoprotein, each subunit consisting of a TA (Tn assembly) domain; 14 ϩ 1/2 epidermal growth factor (EGF)-like domains, a variable number of fibronectin type III (FN III) repeats, and a C-terminal fibrinogen-related domain (FBG). [17][18][19][20][21] The size of Tn-C monomers varies as a result of alternative splicing in the FN III repeats at the pre-mRNA level. There are eight conserved FN III repeats (designated as numbers 1-8) and, in the case of human Tn-C, up to nine alternatively spliced FN III repeats (designated as letters A-D) inserted between the conserved repeats 5 and 6. In adults, the smallest Tn-C variant in which the alternatively splic...

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Involvement of Large Tenascin-C Splice Variants in Breast Cancer Progression

Tsunoda

Inada

Kalembeyi

et al. 2003

The American Journal of Pathology

104

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“…More surprisingly, FibRas cells failed to deposit TN-C in the ECM, although these cells secrete TN-C and produced an ECM containing both FN and perlecan even in the absence of TGFb1 (Figures 3b and 7c). Therefore, oncogenic Ha-Ras not only prevents secretion but also interferes with ECM deposition of TN-C and its direct interaction with FN/perlecan, described in other cell systems (Chiquet-Ehrismann et al, 1991;Chung and Erickson, 1997).…”

Section: Tenascin-c Expression Is Downregulated In Eph4 Cells Upon Epmentioning

confidence: 96%

Enhanced tenascin-C expression and matrix deposition during Ras/TGF-β-induced progression of mammary tumor cells

et al. 2004

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Overexpression of tenascin-C (TN-C) in breast carcinomas has been associated with a migratory or even invasive tumor cell phenotype. The mechanisms regulating expression and matrix deposition of TN-C in normal and cancerous breast tissues are, however, little understood. Here, we demonstrate that mouse mammary epithelial cells (EpH4) transformed by oncogenic Ha-Ras (EpRas) overexpress TN-C, which accumulates in the cytoplasm. When EpRas cells undergo epithelial-mesenchymal transition (EMT) in response to TGFb1, they secrete TN-C into the culture medium. In EpRas cells undergoing TGFb1-induced EMT in three-dimensional (3D)-collagen gel cultures, TN-C was deposited into an extracellular matrix (ECM) already containing fibronectin and perlecan. Under less physiological 2D plastic cultures, EpRas cells undergoing EMT failed to deposit TN-C into an (apparently incomplete) ECM. Ras-downstream signaling was dissected by pharmacological inhibitors and effectorspecific Ras mutants (V12S35, V12C40), specifically inhibiting or activating ERK/MAPK or PI3K signaling, respectively. We showed that TN-C overexpression required a hyperactive ERK/MAPK-signaling pathway, while elevated PI3K signaling did not enhance TN-C expression. Similarly, tumors induced by cells exhibiting hyperactive ERK/MAPK signaling showed expression of TN-C in the tumor cells themselves, while only endothelial cells expressed TN-C in tumors caused by the V12C40 mutant (incapable of EMT in vivo). Taken together, our data indicate that hyperactive ERK/MAPK signaling causes enhanced expression of TN-C, while its secretion is induced by TGFb1 and both signals cooperate in TN-C matrix deposition. Importantly, both signals also cooperate to induce EMT in vitro and tumor progression/ metastasis in vivo.

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“…The three isoforms of chick tenascin, Tn230, Tn200, and Tn190, display tissue-specific distributions in vivo (Prieto et al, 1990;Chiquet-Ehrismann et al, 1991). To determine which tenascin isoform was present in the tissues examined above, longitudinal sections of Day 19 chick embryo knee were processed for immunofluorescence using anti-Tn26 and anti-Tn32 monoclonal antibodies (Spring et al, 1989).…”

Section: Tenascin Isoformsmentioning

confidence: 99%

“…Tenascin variants differing in molecular size have been found in both mammals and avians; they are the product of alternative splicing and differ in the number of fibronectin type I11 repeats (Spring et al, 1989;Gulcher et al, 1989;Prieto et al, 1990;Saga et al, 1991;Siri et al, 1991;Weller et al, 1991). In chick the largest tenascin has 13 such repeats and an Mr of 230,000 (Tn230), whereas variants with only nine or eight repeats exhibit Mr's of 200,000 (Tn200) and 190,000 (Tn190), respectively (Spring et al, 1989;Chiquet-Ehrismann et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Tenascin is associated with articular cartilage development

Pacifici

Iwamoto

Golden

et al. 1993

Developmental Dynamics

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The roles of tenascin in cartilage development and function remain unclear. Based on the observation that tenascin is particularly abundant at the epiphyseal extremities of developing cartilaginous models of long bones in chick and mouse embryo, we tested the hypothesis that tenascin is involved in articular cartilage development. Immunofluorescence analysis revealed that tenascin was first localized in the cell condensation region of Day 4 chick embryo limb buds, where the cartilaginous models form. With further development, tenascin gene expression became indeed restricted to the articular cap of the models. Tenascin persisted in the articular cartilage of postnatal chickens but appeared to decrease with age. The protein was also abundant in embryonic and adult tracheal cartilage rings which, like articular cartilage, persist throughout postnatal life. Similar patterns of tenascin expression were seen in mouse. Using monoclonal antibodies to avian tenascin variants, we found that the bulk of articular cartilage contained the shortest tenascin variant (Tn190), whereas the largest variant (Tn230) was present in tissues associated or interacting with articular cartilage (ligaments and meniscus). The protein and its mRNA, however, were undetectable in growth plate cartilage undergoing maturation and endochondral ossification. This inverse correlation between chondrocyte maturation and tenascin production was corroborated by the finding that tenascin gene expression decreased markedly during maturation of chondrocytes in culture and during formation of a secondary ossification center within the articular cap in vivo. Thus, tenascin is intimately associated with the development of articular cartilage and other permanent cartilages whereas absence or reduced amounts of this matrix protein characterize transient cartilages which undergo maturation and are replaced by bone.0 1993 Wiley-Liss, Inc.

show abstract

Tenascin variants: differential binding to fibronectin and distinct distribution in cell cultures and tissues.

Cited by 146 publications

References 35 publications

Involvement of Large Tenascin-C Splice Variants in Breast Cancer Progression

Involvement of Large Tenascin-C Splice Variants in Breast Cancer Progression

Enhanced tenascin-C expression and matrix deposition during Ras/TGF-β-induced progression of mammary tumor cells

Tenascin is associated with articular cartilage development

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