Tenascin-C is a member of the matricellular protein family, and its expression level is correlated to poor prognosis in cancer, including glioblastoma, whereas its substantial role in tumor formation and malignant progression remains controversial. We reported previously that peptide TNIIIA2 derived from the cancer-associated alternative splicing domain of tenascin-C molecule has an ability to activate b1-integrin strongly and to maintain it for a long time. Here, we demonstrate that b1-integrin activation by TNIIIA2 causes acquisition of aggressive behavior, dysregulated proliferation, and migration, characteristic of glioblastoma cells. TNIIIA2 hyperstimulated the platelet-derived growth factor-dependent cell survival and proliferation in an anchorage-independent as well as-dependent manner in glioblastoma cells. TNIIIA2 also strongly promoted glioblastoma multiforme cell migration, which was accompanied by an epithelial-mesenchymal transition-like morphologic change on the fibronectin substrate. Notably, acquisition of these aggressive properties by TNIIIA2 in glioblastoma cells was abrogated by peptide FNIII14 that is capable of inducing inactivation in b1-integrin activation. Moreover, FNIII14 significantly inhibited tumor growth in a mouse xenograft glioblastoma model. More importantly, FNIII14 sensitized glioblastoma cells to temozolomide via downregulation of O 6-methylguanine-DNA methyltransferase expression. Consequently, FNIII14 augmented the antitumor activity of temozolomide in a mouse xenograft glioblastoma model. Taken altogether, the present study provides not only an interpretation for the critical role of tenascin-C/TNIIIA2 in aggressive behavior of glioblastoma cells, but also an important strategy for glioblastoma chemotherapy. Inhibition of the tenascin-C/b1-integrin axis may be a therapeutic target for glioblastoma, and peptide FNIII14 may represent a new approach for glioblastoma chemotherapy. Significance: These findings provide a proposal of new strategy for glioblastoma chemotherapy based on integrin inactivation.

Background:The tenascin-C-derived peptide TNIIIA2 is capable of activating ␤1-integrins. Results: TNIIIA2 greatly enhanced cell survival and PDGF-dependent proliferation through potentiated and sustained activation of integrin ␣5␤1, resulting in continuous proliferation even after reaching confluency. Conclusion: TNIIIA2-induced integrin ␣5␤1 activation causes deregulated cell growth. Significance: These results offer a new insight into the physiological/pathological role of tenascin-C in tissues where it is highly expressed.

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A bidentate ligand, 3-aminopropanethiolate (apt), was synthesized and treated with RhCl 3 ·3H 2 O in basic water to yield a novel mononuclear complex, fac(S)- [Rh(apt) 3+ (2b), which were characterized by stereochemical, spectrochemical, and electrochemical methods. 2a and 2b are stable and exhibit trivalency in water. X-ray crystallographic analysis of 2a and 2b showed that all of the bridging sulfur atoms are fixed in the R configuration for the ∆ unit and in the S configuration for the Λ unit, and each complex has six six-membered chelate rings, all of which are in the chair conformation. The crystal structure of the corresponding 2-aminoethanethiolate (aet) trinuclear complex ∆Λ-[Co{Rh(aet) 3 } 2 ] 3+ (4a) was also deter-

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