Integrin β3 and CD44 levels determine the effects of the OPN-a splicing variant on lung cancer cell growth

Sun, Shih-Jung; Wu, Chun-Chi; Sheu, Gwo‐Tarng; Chang, Haṡok; Chen, Meiyu; Lin, Ying‐Chu; Chuang, Chun‐Yi; Hsu, Shih-Lan; Chang, Jinghua Tsai

doi:10.18632/oncotarget.10865

Cited by 31 publications

(20 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data explain the results of previous studies implicating osteopontin in tumor cells, as well as its receptor CD44 on host cells, in metastasis to other sites. 15,44,45 Furthermore, our results bear clinical implications for selective osteopontin isoform targeting, since selective sSPP1 inhibition can be accomplished using protein and RNAbased methods. 35 Furthermore, sSPP1 is identified to exert its pro-metastatic function by regulating tumor-to-host CCL2/CCR2 signaling.…”

Section: Discussionmentioning

confidence: 80%

Tumor-derived osteopontin isoforms cooperate with TRP53 and CCL2 to promote lung metastasis

et al. 2016

View full text Add to dashboard Cite

The lungs are ubiquitous receptacles of metastases originating from various bodily tumors. Although osteopontin (SPP1) has been associated with tumor dissemination, the role of its isoforms in lung-directed metastasis is incompletely understood. We employed syngeneic mouse models of spontaneous and induced lung-targeted metastasis in C57BL/6 mice competent and deficient in both Spp1 alleles. Tumorderived osteopontin expression was modulated using either stable anti-Spp1 RNA interference, or forced overexpression of intracellular and secreted Spp1 isoforms. Identified osteopontin's downstream partners were validated using lung adenocarcinoma cells conditionally lacking the Trp53 gene and Ccr2-deficient mice. We determined that host-derived osteopontin was dispensable for pulmonary colonization by different tumor types. Oppositely, tumor-originated intracellular osteopontin promoted tumor cell survival by preventing tumor-related protein 53-mediated apoptosis, while the secretory osteopontin functioned in a paracrine mode to accelerate lung metastasis by enhancing tumor-derived C-C-motif chemokine ligand 2 signaling to cognate host receptors. As new ways to target osteopontin signaling are becoming available, the cytokine may constitute an important therapeutic target against pulmonary involvement by cancers of other organs. KEYWORDSC-C-motif chemokine ligand 2; inflammation and cancer; secreted phosphoprotein 1; spontaneous lung metastasis; tumor-related protein 53

show abstract

Section: Discussionmentioning

confidence: 80%

Tumor-derived osteopontin isoforms cooperate with TRP53 and CCL2 to promote lung metastasis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Secreted OPN activates the NF-kappa B signaling pathway primarily by binding to integrin αvβ3 and eventually results in tumor progression 25 - 27 . Interestingly, OPN was shown to increase tumor growth via activation of the CD44/NF-kappa B pathway in cells with low integrin β3 levels in breast cancer 28 . However, it is still unclear whether the NF-kappa B signaling pathway is involved in secreted OPN-mediated HNC progression.…”

Section: Introductionmentioning

confidence: 99%

Cancer-associated Fibroblast-derived IL-6 Promotes Head and Neck Cancer Progression via the Osteopontin-NF-kappa B Signaling Pathway

et al. 2018

View full text Add to dashboard Cite

Osteopontin (OPN), a chemokine-like protein, plays a crucial role in the proliferation and metastasis of various cancers. However, how tumor stroma modulates the expression of neoplastic OPN and the multifaceted roles of OPN in head and neck cancer (HNC) are unclear. In this study, we tried to investigate the bridging role of OPN between tumor stroma and cancer cells.Methods: Immunohistochemical staining and quantitative real-time PCR were used to detect OPN expression in HNC tissues, and the correlations between OPN expression and clinicopathologic features were then analyzed. We used a co-culture assay to study the modulatory role of IL-6 on OPN expression and immunoprecipitation analysis was used to determine the endogenous interaction between OPN and integrin αvβ3. Furthermore, a xenograft assay was carried out to confirm the tumor-promoting role and the potential therapeutic value of OPN in HNC.Results: We found that OPN was significantly up-regulated in HNCs, and the elevated OPN was correlated with poor prognosis. Moreover, we identified IL-6 secreted by cancer-associated fibroblasts (CAFs) as the major upstream molecule that triggers the induction of neoplastic OPN. As such, during the interaction of fibroblasts and cancer cells, the increased neoplastic OPN induced by stromal IL-6 accelerated the growth, migration and invasion of cancer cells. More importantly, we also showed that soluble OPN could promote HNC progression via the integrin αvβ3-NF-kappa B pathway, and the combination of OPN and IL-6 had a better prognostic and diagnostic performance in HNC than either molecule alone.Conclusion: Our study identified a novel modulatory role for OPN in HNC progression and further demonstrated that the combination of OPN and IL-6 might be a promising prognostic and diagnostic indicator as well as a potential cancer therapeutic target.

show abstract

“…Integrin receptors comprise an α-subunit and a β-subunit, which can give rise to numerous subtypes (e.g., αvβ3, αvβ1, αvβ5, αvβ6, α8β1, and α5β1) that bind with Arginine-Glycine-Aspartate (RGD) sequences in proteins. In addition, there are other integrin subtypes (e.g., α4β1, α9β1, and α4β7) that can bind to the Serine-Valine-Valine-Tyrosine-Glutamic-Leucine-Arginine (SWYGL) sequences on OPN [9-11]. Receptors on the cell surface can integrate with OPN and then induce multiple signal transfer pathways and gene expression, and can alter the basic activity of tumor cells, including metastasis, invasion, and apoptosis [12-14].…”

Section: Introductionmentioning

confidence: 99%

Osteopontin Promotes Cell Migration and Invasion, and Inhibits Apoptosis and Autophagy in Colorectal Cancer by activating the p38 MAPK Signaling Pathway

Huang

Quan

Chen

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: Osteopontin (OPN) is highly expressed in colorectal cancer (CRC) and is associated with disease progression in vivo. High levels of OPN have been demonstrated to predict low survival rates in CRC. Autophagy is a process of self-digestion, which is thought to play a significant role in carcinogenesis. However, the mechanisms of OPN's effects on CRC cell autophagy have not been elucidated. Therefore, we aimed to investigate possible mechanisms of OPN's effects on CRC autophagy. Methods: HCT116 cell proliferation, apoptosis, and migration and invasion ability were identified by cell counting k¡t-8 assay, flow cytometry, wound healing assay, and transwell chamber invasion assay, respectively. The ratios of proteins LC3-II/LC3-I, P62, and Atg7 were analyzed by Western-blot. Expressions of Beclin-1, Atg4b, Bnip3, and Vps34, both in transcriptional and translational levels, were analyzed and compared by RT-PCR and Western blot. Immunofluorescence and co-focusing experiments were used to investigate the formation of autophagosomes. Results: The results showed that OPN can promote cell proliferation, migration, and invasion, as well as inhibit cell apoptosis. It was also demonstrated that OPN could inhibit cell autophagy. Further experiments revealed that the inhibitory effect of OPN on autophagy could be reversed by blocking the p38 MAPK pathway in HCT116 cells. Conclusion: OPN is involved in HCT116 cell progression and is capable of inhibiting cell autophagy possibly by activating the p38 MAPK signaling pathway, implying that OPN could be a potential novel molecular therapeutic biomarker in patients with CRC.

show abstract

Integrin β3 and CD44 levels determine the effects of the OPN-a splicing variant on lung cancer cell growth

Cited by 31 publications

References 32 publications

Tumor-derived osteopontin isoforms cooperate with TRP53 and CCL2 to promote lung metastasis

Tumor-derived osteopontin isoforms cooperate with TRP53 and CCL2 to promote lung metastasis

Cancer-associated Fibroblast-derived IL-6 Promotes Head and Neck Cancer Progression via the Osteopontin-NF-kappa B Signaling Pathway

Osteopontin Promotes Cell Migration and Invasion, and Inhibits Apoptosis and Autophagy in Colorectal Cancer by activating the p38 MAPK Signaling Pathway

Contact Info

Product

Resources

About