Involvement of tenascin-C in proliferation and migration of laryngeal carcinoma cells

Abstract

Tenascin-C (TN-C) is an extracellular matrix glycoprotein upregulated in various pathological processes. In this study, we investigated its distribution in dysplasia and carcinoma of the human larynx using immunohistochemistry and in situ hybridization (ISH) techniques. In all cancer tissues, TN-C immunostaining was markedly increased in the stroma, especially around the cancer cell nests. In addition, cytoplasmic staining of cancer cells was also observed in 62.5% of the invasive cases, the cells being distributed in the periphery of the nests adjacent to the stroma. TN-C mRNA signals in cancer cells were detected in all six cases examined by ISH. Furthermore, in vitro evaluation of the roles of TN-C demonstrated an increase in the proliferating cell fraction in a dose-dependent manner. In a wound closure assay, the addition of TN-C promoted migration. We conclude that TN-C secreted by cancer cells may be involved in their proliferation and migration in an autocrine fashion.

Tenascin C Induces Epithelial-Mesenchymal Transition–Like Change Accompanied by SRC Activation and Focal Adhesion Kinase Phosphorylation in Human Breast Cancer Cells

“…10,35,36 MCF-7 cells under the TNC condition showed faster migration in wound closure as previously reported using other cell lines. 22,25 In conclusion, we have demonstrated that TNC is preferentially deposited in the stroma with scattered and small cancer nests in vivo and induces EMT-like change showing loss of cell-cell junctions and gain of migratory behaviors in breast cancer cells in vitro. The cancer cell phenotype could be dynamically converted by spatiotemporal expression of TNC.…”

“…The TNC had been purified from conditioned medium of human glioma cell line U251MG as previously described. 22 After 16 hours of incubation, 5 ng/ml TGF-␤1 (Roche Diagnostics, Mannheim, Germany) was added and the cells were cultured for another 48 hours. Neutralizing antibodies for the ␣v integrin subunit (AV1, 1:40; Millipore Corporation, Billerica, MA) or ␤1 (P4C10, 5 g/ml; Millipore) and the SRC kinase inhibitor (pp2, 10 mol/L, Calbiochem, La Jolla, CA) were added to the medium when the cells were plated.…”

“…22 The wells of 12-well plates were incubated with 20 g of TNC per well for 1 hour. The suspension of MCF-7 cells (1 ϫ 10 6 cells/well) was poured into a well and grown until subconfluence and further incubated with or without 5 ng/ml TGF-␤1 for 24 hours.…”

“…19,20 Immunohistochemical studies of invasive ductal carcinoma cases have demonstrated that expression is indicative of a poorer patient outcome. 21 It has been reported that TNC promotes proliferation and migratory activity of cancer cells [22][23][24][25] and up-regulates the expression of matrix metalloproteinases by breast cancer cells. 24,26 Furthermore, it is important to note that TNC expression is frequently observed in invasion borders of cancer tissues and in microinvasive foci around intraductal carcinomas, where cells may undergo EMT.…”

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

“…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][13][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.…”