Osteopontin-c splicing isoform contributes to ovarian cancer progression.

作者: Tatiana M Tilli , Vanessa Ferreira Franco , Bruno Kaufmann Robbs , Joao Luiz Mendes Wanderley , Fabrício Ribeiro de Azevedo da Silva

DOI: 10.1158/1541-7786.MCR-10-0463

关键词:

摘要: Ovarian carcinoma is one of the most aggressive gynecological diseases and generally diagnosed at advanced stages. Osteopontin (OPN) proteins overexpressed in ovarian cancer involved tumorigenesis metastasis. Alternative splicing OPN leads to 3 isoforms, OPNa, OPNb, OPNc. However, expression pattern roles each these isoforms have not been previously characterized cancer. Herein, we evaluated profiling tumor nontumor samples their putative biology using vitro vivo functional assays. OPNa OPNb were expressed both samples, whereas OPNc was specifically samples. The isoform significantly activated OvCar-3 cell proliferation, migration, invasion, anchorage-independent growth formation vivo. Additionally, also shown that some OPNc-dependent protumorigenic are mediated by PI3K/Akt signaling pathway. stimulated immortalized epithelial IOSE indicating a role for this tumorigenesis. Functional assays conditioned medium an anti-OPNc antibody cellular effects observed herein promoted secreted According our data, OPNc-specific its on favoring different aspects progression suggest contributes physiopathology Altogether, data open possibilities new therapeutic approaches selectively down regulate OPNc, altering properties progression.

参考文章(52)
M Wendel, G Andersson, M Flores, B Ek-Rylander, D Heinegård, Dephosphorylation of osteopontin and bone sialoprotein by osteoclastic tartrate-resistant acid phosphatase. Modulation of osteoclast adhesion in vitro. Journal of Biological Chemistry. ,vol. 269, pp. 14853- 14856 ,(1994) , 10.1016/S0021-9258(17)36541-9
Lynn M. Matrisian, Howard C. Crawford, Lucy Liaw, Lucy Liaw, Distinct roles of osteopontin in host defense activity and tumor survival during squamous cell carcinoma progression in vivo Cancer Research. ,vol. 58, pp. 5206- 5215 ,(1998)
Kwong-Kwok Wong, Rita S. Cheng, Samuel C. Mok, Identification of differentially expressed genes from ovarian cancer cells by MICROMAX™ cDNA microarray system BioTechniques. ,vol. 30, pp. 670- 675 ,(2001) , 10.2144/01303DD05
Yan Huang, Keqin Hua, Xianrong Zhou, Hongyan Jin, Xiaojun Chen, Xin Lu, Yinhua Yu, Xiliang Zha, Youji Feng, Activation of the PI3K/AKT pathway mediates FSH-stimulated VEGF expression in ovarian serous cystadenocarcinoma. Cell Research. ,vol. 18, pp. 780- 791 ,(2008) , 10.1038/CR.2008.70
Mana Mirza, Elizabeth Shaughnessy, John K. Hurley, Kristie A. Vanpatten, Gary A. Pestano, Bin He, Georg F. Weber, Osteopontin-c is a selective marker of breast cancer. International Journal of Cancer. ,vol. 122, pp. 889- 897 ,(2008) , 10.1002/IJC.23204
Sergey V. Ivanov, Alla V. Ivanova, Chandra M.V. Goparaju, Yuanbin Chen, Amanda Beck, Harvey I. Pass, Tumorigenic properties of alternative osteopontin isoforms in mesothelioma. Biochemical and Biophysical Research Communications. ,vol. 382, pp. 514- 518 ,(2009) , 10.1016/J.BBRC.2009.03.042
Michael C. Kiefer, Diane M. Bauer, Philip J. Barr, The cDNA and derived amino acid sequence for human osteopontin. Nucleic Acids Research. ,vol. 17, pp. 3306- 3306 ,(1989) , 10.1093/NAR/17.8.3306
C. Blake Gilks, Jaime Prat, Ovarian carcinoma pathology and genetics: recent advances Human Pathology. ,vol. 40, pp. 1213- 1223 ,(2009) , 10.1016/J.HUMPATH.2009.04.017
Motoki Matsuura, Takahiro Suzuki, Tsuyoshi Saito, Osteopontin is a new target molecule for ovarian clear cell carcinoma therapy. Cancer Science. ,vol. 101, pp. 1828- 1833 ,(2010) , 10.1111/J.1349-7006.2010.01615.X
T. Nishio, S. Kawaguchi, M. Yamamoto, T. Iseda, T. Kawasaki, T. Hase, Tenascin-C regulates proliferation and migration of cultured astrocytes in a scratch wound assay. Neuroscience. ,vol. 132, pp. 87- 102 ,(2005) , 10.1016/J.NEUROSCIENCE.2004.12.028