[PubMed] [Google Scholar] 12

[PubMed] [Google Scholar] 12. results indicate that CLIC1 is an important contributor to tumor invasion, metastasis and angiogenesis. Implications This study uncovers an important new function of CLIC1 in the regulation of cell-extracellular matrix interactions and ability of tumor cells to metastasize to distant organs. results, we found that knockdown of CLIC1 significantly reduced experimental lung metastasis, suggesting that CLIC1-mediated functions are necessary alpha-Boswellic acid for efficient tumor cell seeding in the lungs. Together, these results show that fibrin-embedded tumor and endothelial cells depend on CLIC1 for invadopodia and colony formation and lung metastasis and that this function correlates with the capacity of CLIC1 to promote lung metastasis and to metastasize to distant organs in vivo. Thus, strategies to inhibit CLIC1 could be useful for the treatment of aggressive cancer. Supplementary Material 1Click here to view.(186K, pdf) ACKNOWLEDGEMENTS We would like to thank Dr. Robert Sobol and Ashley Brown from the UPCI Vector Core Facility for constructing shRNA vectors. This project used the UPCI Cell and Tissue Imaging Facility, UPCI Animal Facility and the UPCI Vector Core Facility, which are supported by the UPCI Cancer Center Support Grant. GRANT alpha-Boswellic acid SUPPORT This work was supported by National Institutes of Health grants CA134330 (JP), 5T32DK007774-14 (LAG), and P30CA047904 (UPCI alpha-Boswellic acid CCSG). Footnotes The authors have no potential conflict of interest. REFERENCES 1. Millien VO, Lu W, Shaw J, Yuan X, Mak G, Roberts L, et al. Cleavage of fibrinogen by proteinases elicits allergic responses through Toll-like receptor 4. Science. 2013;341:792C796. [PMC free article] [PubMed] [Google Scholar] 2. van den Berg YW, van den Hengel LG, Myers HR, Ayachi O, Jordanova E, Ruf W, et al. Alternatively spliced tissue factor induces angiogenesis through integrin ligation. Proc Natl Acad Sci U S A. 2009;106:19497C19502. [PMC free article] [PubMed] [Google Scholar] 3. Drew AF, Liu H, Davidson JM, Daugherty CC, Degen JL. Wound-healing defects in mice lacking fibrinogen. Blood. 2001;97:3691C3698. [PubMed] [Google Scholar] 4. Palumbo JS, Talmage KE, Massari JV, La Jeunesse CM, Flick MJ, Kombrinck KW, et al. Platelets and fibrin(ogen) increase metastatic potential by impeding Rabbit polyclonal to Smac natural killer cell-mediated elimination of tumor cells. Blood. 2005;105:178C185. [PubMed] [Google Scholar] 5. Mosesson MW. Fibrinogen and fibrin structure and functions. J Thromb Haemost. 2005;3:1894C1904. [PubMed] [Google Scholar] 6. Knowles LM, Gurski LA, Engel C, Gnarra JR, Maranchie JK, Pilch J. Integrin alphavbeta3 and fibronectin upregulate Slug in alpha-Boswellic acid cancer cells to promote clot invasion and metastasis. Cancer Res. 2013;73:6175C6184. [PMC free article] [PubMed] [Google Scholar] 7. Malik G, Knowles LM, Dhir R, Xu S, Yang S, Ruoslahti E, et al. Plasma fibronectin promotes lung metastasis by contributions to fibrin clots and tumor cell invasion. Tumor Res. 2010;70:4327C4334. [PMC free article] [PubMed] [Google Scholar] 8. Liu J, Tan Y, Zhang H, Zhang Y, Xu P, Chen J, et al. Soft fibrin gels promote selection and growth of tumorigenic cells. Nat Mater. 2012;11:734C741. [PMC free article] [PubMed] [Google Scholar] 9. Knowles LM, Malik G, Hood BL, Conrads TP, Pilch J. CLT1 focuses on angiogenic endothelium through CLIC1 and fibronectin. Angiogenesis. 2012;15:115C129. [PMC free article] [PubMed] [Google Scholar] 10. Hill JJ, Tremblay TL, Pen A, Li J, Robotham AC, Lenferink AE, et al. Recognition of vascular breast tumor markers by laser capture microdissection and label-free LC-MS. J Proteome Res. 2011;10:2479C2493. [PubMed] [Google Scholar] 11. Li RK, Zhang J, Zhang YH, Li ML, Wang M, Tang JW. Chloride intracellular channel 1 is an important factor in the lymphatic metastasis of hepatocarcinoma. Biomed Pharmacother. 2012;66:167C172. [PubMed] [Google Scholar] 12. Wang W, Xu X, Shao W, Li L, Yin W, Xiu L, et al. The manifestation and medical significance of CLIC1 and HSP27 in lung adenocarcinoma. Tumour Biol. 2011;32:1199C1208. alpha-Boswellic acid [PubMed] [Google Scholar] 13. Tang HY, Ale LA, Tanyi JL, Zhang R, Liu Q, Speicher DW. Protein isoform-specific validation defines multiple chloride intracellular channel and tropomyosin isoforms as serological biomarkers of ovarian malignancy. J Proteomics. 2013;89:165C178. [PMC free article] [PubMed] [Google Scholar] 14. Zheng DL, Huang QL, Zhou F, Huang QJ, Lin JY, Lin X. PA28beta regulates cell invasion of gastric malignancy via modulating the manifestation of chloride intracellular channel 1. J Cell Biochem. 2012;113:1537C1546. [PubMed] [Google Scholar] 15. Tung JJ, Kitajewski J. Chloride intracellular channel 1 functions in endothelial cell growth and migration. J Angiogenes Res. 2010;2:23. [PMC free article] [PubMed] [Google Scholar] 16. Schwarzbauer JE, Sechler JL. Fibronectin fibrillogenesis: a paradigm for extracellular matrix assembly..