Meet the Tenascins: Multifunctional and Mysterious

Hsia, Henry C.; Schwarzbauer, Jean E.

doi:10.1074/jbc.r500005200

Cited by 148 publications

(120 citation statements)

References 51 publications

(56 reference statements)

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“…We found that only early stage CMBs (<7 d), before the setting of a boundary, could be homogenously fused and induced into chondrogenic differentiation and the formation of large and functional cartilage tissues. These findings are consistent with the reported role of tenascin-C in modulating cell attachment to fibronectin (30,31).…”

Section: Discussionsupporting

confidence: 82%

Large, stratified, and mechanically functional human cartilage grown in vitro by mesenchymal condensation

Bhumiratana

Eton

Oungoulian

et al. 2014

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

169

191

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The efforts to grow mechanically functional cartilage from human mesenchymal stem cells have not been successful. We report that clinically sized pieces of human cartilage with physiologic stratification and biomechanics can be grown in vitro by recapitulating some aspects of the developmental process of mesenchymal condensation. By exposure to transforming growth factor-β, mesenchymal stem cells were induced to condense into cellular bodies, undergo chondrogenic differentiation, and form cartilagenous tissue, in a process designed to mimic mesenchymal condensation leading into chondrogenesis. We discovered that the condensed mesenchymal cell bodies (CMBs) formed in vitro set an outer boundary after 5 d of culture, as indicated by the expression of mesenchymal condensation genes and deposition of tenascin. Before setting of boundaries, the CMBs could be fused into homogenous cellular aggregates giving rise to well-differentiated and mechanically functional cartilage. We used the mesenchymal condensation and fusion of CMBs to grow centimeter-sized, anatomically shaped pieces of human articular cartilage over 5 wk of culture. For the first time to our knowledge biomechanical properties of cartilage derived from human mesenchymal cells were comparable to native cartilage, with the Young's modulus of >800 kPa and equilibrium friction coeffcient of <0.3. We also demonstrate that CMBs have capability to form mechanically strong cartilage-cartilage interface in an in vitro cartilage defect model. The CMBs, which acted as "lego-like" blocks of neocartilage, were capable of assembling into human cartilage with physiologic-like structure and mechanical properties.

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Section: Discussionsupporting

confidence: 82%

Large, stratified, and mechanically functional human cartilage grown in vitro by mesenchymal condensation

Bhumiratana

Eton

Oungoulian

et al. 2014

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

169

191

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“…TnC is related to many important cell functions, such as adhesion, migration, development and tumor metastasis [21]. TnC splicing isoforms contain the insertion of FnIII domains between constitutive domains FnIII 5 and FnIII 6 [22].…”

Section: Splice Variants Of Genes In Response To Mechanical Stressmentioning

confidence: 99%

Mechano-Regulation of Alternative Splicing

Liu¹,

Tang²

2013

Current Genomics

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Alternative splicing contributes to the complexity of proteome by producing multiple mRNAs from a single gene. Affymetrix exon arrays and experiments in vivo or in vitro demonstrated that alternative splicing was regulated by mechanical stress. Expression of mechano-growth factor (MGF) which is the splicing isoform of insulin-like growth factor 1(IGF-1) and vascular endothelial growth factor (VEGF) splicing variants such as VEGF121, VEGF165, VEGF206, VEGF189, VEGF165 and VEGF145 are regulated by mechanical stress. However, the mechanism of this process is not yet clear. Increasing evidences showed that the possible mechanism is related to Ca2+ signal pathway and phosphorylation signal pathway. This review proposes possible mechanisms of mechanical splicing regulation. This will contribute to the biomechanical study of alternative splicing.

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“…TNC is secreted from the cells and localized to the extracellular matrix in tumor microenvironments or to stromal cells surrounding tumor cells, so its exuberant expression appears to play a role in tumor progression by regulating cell adhesion and migration (Orend, 2005;Orend and Chiquet-Ehrismann, 2006). Even though the exact roles of TNC in tumorigenesis remain to be determined, the prominent expression of the protein in tumor tissues may potentially provide an excellent opportunity for targeting tumor sites for diagnosis and treatment of diverse solid tumors in vivo (Hsia and Schwarzbauer, 2005).…”

Section: Introductionmentioning

confidence: 99%

Selection and Characterization of Tenascin C Targeting Peptide

Kim

Choi

et al. 2012

Molecules and Cells

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Since tenascin C is a factor expressed highly in the tumorassociated matrix, it would be a desirable first step for targeting the tumor-specific microenvironment. In fact, a high level of tenascin C expression has been reported in most solid tumors, including lung cancer, colon cancer and glioblastoma. Therefore, the targeted binding of tenascin C in tumor stroma would inhibit tumor metastasis by modulating cancer cell growth and migration. We isolated a peptide that bound to tenascin C by phage display peptide library selection, and the selected peptide specifically recognized tenascin C protein in xenograft mouse tissue. We also observed exclusive staining of tenascin C by the selected peptide in tumor patient tissues. Moreover, the peptide reduced tenascin C-induced cell rounding and migration. We propose that the tenascin C targeting peptide may be useful as a specific anti-cancer diagnostic and therapeutic tool for most human solid tumors.

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Meet the Tenascins: Multifunctional and Mysterious

Cited by 148 publications

References 51 publications

Large, stratified, and mechanically functional human cartilage grown in vitro by mesenchymal condensation

Large, stratified, and mechanically functional human cartilage grown in vitro by mesenchymal condensation

Mechano-Regulation of Alternative Splicing

Selection and Characterization of Tenascin C Targeting Peptide

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