Osteopontin Knockdown Suppresses Tumorigenicity of Human Metastatic Breast Carcinoma, MDA-MB-435
Lalita A. Shevde,Lalita A. Shevde,Rajeev S. Samant,Rajeev S. Samant,Jason C. Paik,Brandon J. Metge,Ann F. Chambers,Graham Casey,Andra R. Frost,Danny R. Welch,Danny R. Welch +10 more
TLDR
Functional evidence is provided that OPN contributes to breast tumor growth as well, in addition to the widely reported roles of OPN in late stages of tumor progression.Abstract:
Elevated expression of osteopontin (OPN), a secreted phosphoglycoprotein, is frequently associated with many transformed cell lines. Various studies suggest that OPN may contribute to tumor progression as well as metastasis in multiple tumor types. High levels of OPN have been reported in patients with metastatic cancers, including breast. We found that the expression of OPN corroborates with the aggressive phenotype of the breast cancer cells i.e. the expression of OPN is acquired as the breast cancer cells become more aggressive. To assess the role(s) of OPN in breast carcinoma, expression of endogenous OPN was knocked down in metastatic MDA-MB-435 human breast carcinoma cells using RNA interference. We targeted multiple regions of the OPN transcript for RNA interference, along with ‘scrambled’ and ‘non-targeting siRNA pool’ controls to distinguish between target-specific and potential off-target effects including interferon-response gene (PeIF2-α) induction. The OPN knockdown by shRNA suppressed tumor take in immunocompromised mice. The ‘silenced’ cells also showed significantly lower invasion and migration in modified Boyden chamber assays and reduced ability to grow in soft agar. Thus, in addition to the widely reported roles of OPN in late stages of tumor progression, these results provide functional evidence that OPN contributes to breast tumor growth as well.read more
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Role of osteopontin in the pathophysiology of cancer.
TL;DR: A broad perspective is provided on the importance of OPN in the pathophysiology of cancer to be a crucial mediator of cellular cross talk and an influential factor in the tumor microenvironment.
Journal ArticleDOI
Integrated pipeline for mass spectrometry-based discovery and confirmation of biomarkers demonstrated in a mouse model of breast cancer
Jeffrey R. Whiteaker,Heidi Zhang,Lei Zhao,Pei Wang,Karen S. Kelly-Spratt,Richard G. Ivey,Brian D. Piening,Li Chia Feng,Erik Kasarda,Kay E. Gurley,Jimmy K. Eng,Lewis A. Chodosh,Christopher J. Kemp,Martin W. McIntosh,Amanda G. Paulovich +14 more
TL;DR: The results show that a staged pipeline employing shotgun-based comparative proteomics for biomarker discovery and multiple reaction monitoring for confirmation of biomarker candidates is capable of finding novel tissue and plasma biomarkers in a mouse model of breast cancer.
Journal ArticleDOI
Metastasis suppressors genes in cancer
TL;DR: The known metastasis suppressors are reviewed and the suspected mechanisms by which they inhibit metastasis are summarized.
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Osteopontin Mediates an MZF1-TGF-β1-Dependent Transformation of Mesenchymal Stem Cells into Cancer Associated Fibroblasts in Breast Cancer
Cynthia E. Weber,Anai N. Kothari,Anai N. Kothari,Philip Y. Wai,Philip Y. Wai,Neill Y. Li,Neill Y. Li,Joseph Driver,Joseph Driver,Matthew A.C. Zapf,Matthew A.C. Zapf,Carrie A. Franzen,Gopal N. Gupta,Gopal N. Gupta,Clodio Osipo,Andrei Zlobin,Wing Kin Syn,Wing Kin Syn,Jiwang Zhang,Paul C. Kuo,Paul C. Kuo,Zhiyong Mi,Zhiyong Mi +22 more
TL;DR: It is concluded that tumor-derived OPN engenders MSC-to-CAF transformation in the microenvironment to promote tumor growth and metastasis via the OPN–MZF1–TGF-β1 pathway.
Journal ArticleDOI
Lentiviral-mediated miRNA against osteopontin suppresses tumor growth and metastasis of human hepatocellular carcinoma.
Bing-Sheng Sun,Qiongzhu Dong,Qing-Hai Ye,Hai-Jing Sun,Hu-Liang Jia,Xiao-Qun Zhu,Dao-Yong Liu,Jie Chen,Qiong Xue,Hai-Jun Zhou,Ning Ren,Lun-Xiu Qin +11 more
TL;DR: In this article, RNA interference mediated by viral vectors was applied to analyze the role of osteopontin in metastasis of hepatocellular carcinoma (HCC), and three lentiviral vectors encoding microRNA against OPN were constructed and found to down-regulate the OPN level by 62, 78, and 95%, respectively, in HCCLM3 cells which had an overexpression of OPN and a higher metastatic potential.
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Role of osteopontin in tumour progression
TL;DR: Growing evidence supports a role for OPN as a potential prognostic factor for various human cancers, and aspects of OPN biology that can complicate interpretation of human studies are considered.