Osteopontin is associated with decreased apoptosis and αv integrin expression in lung adenocarcinoma

Štemberger, Christophe; Matušan-Ilijaš, Koviljka; Avirović, Manuela; Bulat-Kardum, Ljiljana; Ivančić, Aldo; Jonjić, Nives; Lučin, Ksenija

doi:10.1016/j.acthis.2013.07.009

Cited by 19 publications

(15 citation statements)

References 30 publications

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“…OPN is associated with decreased apoptosis in lung adenocarcinoma (Stemberger et al, 2013). In human lung cancer cells, OPN knockdown suppressed lung cancer cell invasion and metastasis and also induced autophagy and abrogated the radioresistance of the cancer cells (B.S.…”

Section: Opn Impacts Pathophysiologies Of Multiple Malignanciesmentioning

confidence: 99%

Role of osteopontin in the pathophysiology of cancer

2014

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Osteopontin (OPN) is a multifunctional cytokine that impacts cell proliferation, survival, drug resistance, invasion, and stem like behavior. Due to its critical involvement in regulating cellular functions, its aberrant expression and/or splicing is functionally responsible for undesirable alterations in disease pathologies, specifically cancer. It is implicated in promoting invasive and metastatic progression of many carcinomas. Due to its autocrine and paracrine activities OPN has been shown to be a crucial mediator of cellular cross talk and an influential factor in the tumor microenvironment. OPN has been implicated as a prognostic and diagnostic marker for several cancer types. It has also been explored as a possible target for treatment. In this article we hope to provide a broad perspective on the importance of OPN in the pathophysiology of cancer.

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Section: Opn Impacts Pathophysiologies Of Multiple Malignanciesmentioning

confidence: 99%

Role of osteopontin in the pathophysiology of cancer

2014

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“…OPN has been shown to interact with several integrins, including α v β 1 , α v β 3 , α v β 5 , α v β 6 , α 8 β 1 and α 5 β 1 [17,18], via the Arg-Gly-Asp (RGD) sequence, and with α 9 β 1 , α 4 β 1 and α 4 β 7 [19,20] via the serine-valine-valine-tyrosine-glutamate-leucine-arginine (SVVYGLR) sequence. The interaction of OPN with cell surface receptors can in turn activate various signal transduction pathways, resulting in changes in gene expression and leading to alterations in cell behavior, including migration, invasion and apoptosis [21,22]. However, although OPN is known to be associated with cell migration and invasion in breast cancer, the precise mechanisms responsible for this role remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Osteopontin Knockdown Inhibits a_v,�₃Integrin-Induced Cell Migration and Invasion and Promotes Apoptosis of Breast Cancer Cells by Inducing Autophagy and Inactivating the PI3K/Akt/mTOR Pathway

Zhang

Guo

Chen

et al. 2014

Cell Physiol Biochem

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Background: Osteopontin (OPN) is associated with tumor formation, progression and metastasis, and increased OPN levels have been associated with poor survival in breast cancer. We investigated the mechanisms responsible for OPN activity, and the relationships between OPN expression and clinical parameters in breast cancer. Methods: OPN mRNA and protein levels were compared in malignant and benign breast tumors by polymerase chain reaction (PCR) and immunohistochemistry, respectively, and levels in breast cancer cells were determined by PCR and western blotting. The effects of lentiviral-mediated knockdown of OPN on OPN and α_v,β₃ integrin expression, cell invasion and migration, autophagy and apoptosis were analyzed in MDA-MB-231 cells. Results: OPN expression increased with aggressiveness of breast cancer phenotype. OPN knockdown inhibited α_v,β₃ integrin expression in MDA-MB-231 cells, with subsequent inhibition of cell migration and invasion. Knockdown also inhibited the PI3K/Akt/mTOR pathway, promoted expression of the autophagy-related gene products LC3 and Beclin 1, and increased apoptosis. OPN expression was positively associated with tumor grade and lymph node metastasis. Conclusion: These results suggest that knockdown of OPN may inhibit breast cancer metastasis by regulating α_v,β₃ integrin expression and inducing autophagy and subsequent inhibition of PI3K/Akt/mTOR signaling, thus providing further insights into the complex mechanisms regulating tumor growth and metastasis.

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“…The samples were then washed with PBS and left for 15 mins in 3% H2O2 for blockage of endogenous peroxidase activity, then treated with 10% bovine fetal serum to prevent non-specific connections. The sections were completely covered by drops of OPN anti-human monoclonal IgG antibody (R&D System, MN, USA, 1:100 dilution) and left for 1 hour [12]. All the samples were washed with PBS and after a secondary antibody IgG (R&D System, MN, USA) stage, a streptavidin peroxidase enzyme complex was applied.…”

Section: Immunohistochemistrymentioning

confidence: 99%