Selection and Characterization of Tenascin C Targeting Peptide

김미영,정선주,Ok Ran Kim,Yong Seok Choi,이희란,박기랑,이춘택,강건욱 한국분자세포생물학회 2012 Molecules and cells Vol.33 No.1

Since tenascin C is a factor expressed highly in the tu-mor-associated 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 re-ported 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.

mTOR Signal Transduction Pathways Contribute to TN-C FNIII A1 Overexpression by Mechanical Stress in Osteosarcoma Cells

Zheng, Lianhe,Zhang, Dianzhong,Zhang, Yunfei,Wen, Yanhua,Wang, Yucai Korean Society for Molecular and Cellular Biology 2014 Molecules and cells Vol.37 No.2

Osteosarcoma is the most common primary malignant bone tumor with a very poor prognosis. Treating osteosarcoma remains a challenge due to its high transitivity. Tenascin-C, with large molecular weight variants including different combinations of its alternative spliced FNIII repeats, is specifically over expressed in tumor tissues. This study examined the expression of Tenascin-C FNIIIA1 in osteosarcoma tissues, and estimated the effect of mechanical stimulation on A1 expression in MG-63 cells. Through immunohistochemical analysis, we found that the A1 protein was expressed at a higher level in osteosarcoma tissues than in adjacent normal tissues. By cell migration assay, we observed that there was a significant correlation between A1 expression and MG-63 cell migration. The relation is that Tenascin-C FNIIIA1 can promote MG-63 cell migration. According to our further study into the effect of mechanical stimulation on A1 expression in MG-63 cells, the mRNA and protein levels of A1 were significantly up-regulated under mechanical stress with the mTOR molecule proving indispensable. Meanwhile, 4E-BP1 and S6K1 (downstream molecule of mTOR) are necessary for A1 normal expression in MG-63 cells whether or not mechanical stress has been encountered. We found that Tenascin-C FNIIIA1 is over-expressed in osteosar-coma tissues and can promote MG-63 cell migration. Furthermore, mechanical stress can facilitate MG-63 cell migration though facilitating A1 overexpression with the necessary molecules (mTOR, 4E-BP1 and S6K1). In con-clusion, high expression of A1 may promote the meta-stasis of osteosarcoma by facilitating MG-63 cell migration. Tenascin-C FNIIIA1 could be used as an indicator in metastatic osteosarcoma patients.

mTOR Signal Transduction Pathways Contribute to TN-C FNIII A1 Overexpression by Mechanical Stress in Osteosarcoma Cells

Lianhe Zheng,Dianzhong Zhang,Yunfei Zhang,Yanhua Wen,Yucai Wang 한국분자세포생물학회 2014 Molecules and cells Vol.37 No.2

Osteosarcoma is the most common primary malignant bone tumor with a very poor prognosis. Treating osteosarcoma remains a challenge due to its high transitivity. Tenascin-C, with large molecular weight variants including different combinations of its alternative spliced FNIII repeats, is specifically over expressed in tumor tissues. This study examined the expression of Tenascin-C FNIIIA1 in osteosarcoma tissues, and estimated the effect of mechanical stimulation on A1 expression in MG-63 cells. Through immunohistochemical analysis, we found that the A1 protein was expressed at a higher level in osteosar-coma tissues than in adjacent normal tissues. By cell migration assay, we observed that there was a significant correlation between A1 expression and MG-63 cell migra-tion. The relation is that Tenascin-C FNIIIA1 can promote MG-63 cell migration. According to our further study into the effect of mechanical stimulation on A1 expression in MG-63 cells, the mRNA and protein levels of A1 were significantly up-regulated under mechanical stress with the mTOR molecule proving indispensable. Meanwhile, 4E-BP1 and S6K1 (downstream molecule of mTOR) are necessary for A1 normal expression in MG-63 cells whether or not mechanical stress has been encountered. We found that Tenascin-C FNIIIA1 is over-expressed in osteosar-coma tissues and can promote MG-63 cell migration. Furthermore, mechanical stress can facilitate MG-63 cell migration though facilitating A1 overexpression with the necessary molecules (mTOR, 4E-BP1 and S6K1). In con-clusion, high expression of A1 may promote the meta-stasis of osteosarcoma by facilitating MG-63 cell migration. Tenascin-C FNIIIA1 could be used as an indicator in metastatic osteosarcoma patients.

Tenascin-C Produced by Oxidized LDL-Stimulated Macrophages Increases Foam Cell Formation through Toll-like Receptor-4

Rui Liu,Lihua Zhang,Yong He,Bo Li,Jun Liu,Yingang Ren,Wei Han,Xing Wang 한국분자세포생물학회 2012 Molecules and cells Vol.34 No.1

Atherosclerosis is a chronic inflammatory disease in which both innate and adaptive immunity are involved. Although there have been major advances in the involve-ment of toll-like receptor 4 (TLR4) and CD36 in the initiation and development of this disease, detailed mechanisms remain unknown. Here, we show that tenascin-C (TN-C) can stimulate foam cell formation and this can be inhibited by a TLR4-blocking antibody or CD36 gene silencing. Our results identify TN-C-TLR4 activation as a common molecular mechanism in oxLDL-stimulated foam cell formation and atherosclerosis. In addition, CD36 is the major scavenger receptor responsible for the TN-C-mediated foam cell formation. Taken together, we have identified that TN-C produced by oxLDL-stimulated macrophages increases foam cell formation through TLR4 and scavenger receptor CD36.

Secreted Tenascin C from Activated Hepatic Stellate Cells Promotes Epithelial-mesenchymal Transition in Hepatic Cancer Cell

( Sae Hwan Lee ),( Hong Jian ),( Xiao Liu ),( Wenyu Lin ),( Raymond T Chung ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: Hepatic stellate cell (HSC) plays a pivotal role in hepatocarcinogenesis through direct effects on hepatocytes and modulation of the peri-tumoral stroma and immune response. A change in HSC secretory phenotype upon activation is closely correlated with increased proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells in vitro studies. Tenascin C (TNC) is a large hexameric extracellular matrix glycoprotein and highly expressed in several solid cancer including HCC. The aim of this study was to investigate the TNC expression by activated human HSC lines and the role of TNC in metastasis of HCC cells. Methods: Two HSC lines, LX2 and TWNT4, were stimulated with transforming growth factor-β for 48 hours and protein expression of TNC in media was evaluated with Western blot and ELISA. LX2 was transfected with TNC siRNA for 48 hours and was continued culture for 48 hours after media change. Huh7, hepatic cancer cell line, were incubated for 24 hours with conditioned media from TNC knockdown LX2. Epithelial-mesenchymal transition (EMT)-related genes expression of Huh7 were estimated by quantitative real-time reverse transcription. Results: TNC mRNA expressions were significantly increased in stimulated LX2 and TWNT4 and TNC protein in the media were also highly expressed in both activated HSC lines. TNC knockdown was successfully observed and TNC protein level was also significantly deceased in the media from TNC siRNA transfected LX2. E-cadherin expression was significantly increased and vimentin expression was decreased in Huh7 treated with conditioned media from TNC knockdown LX2. Conclusions: TNC expression was significantly increased in activated human HSC lines and secreted TNC from LX2 promote upregulation EMT in Huh7.

The in vitro analysis of migration and polarity of blastema cells in the extracellular matrix derived from bovine mesenteric in the presence of fibronectin

Kamelia Kohannezhad,Soroush Norouzi,Maryam Tafazoli,Safoura Soleymani,Nasser Mahdavi Shahri,Amin Tavassoli 대한해부학회 2022 Anatomy & Cell Biology Vol.55 No.2