Osteopontin as a therapeutic target for cancer

Bandopadhyay, Monalisa; Bulbule, Anuradha; Butti, Ramesh; Chakraborty, Goutam; Ghorpade, Priyanka; Ghosh, Pompom; Gorain, Mahadeo; Kale, Smita; Kumar, Dhiraj; Kumar, Santosh; Totakura, Kumar V.S.; Roy, Gaurab; Sharma, Priyanka; Shetti, Dattatrya; Soundararajan, Gowrishankar; Thorat, Dhanashri; Tomar, Deepti; Nalukurthi, Radha; Raja, Remya; Mishra, Rajneesh Kumar; Yadav, Amit Singh; Kundu, Gopal C.

doi:10.1517/14728222.2014.925447

Cited by 117 publications

(104 citation statements)

References 92 publications

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“…Thus, our findings bear potential clinical implications, as several approaches to inhibit osteopontin signaling are in development. 34,35 Our negative results from osteopontin-deficient mice are different from findings from breast cancer and malignant pleural effusion (MPE) models where host osteopontin was important. 15,16 However, the different results can be reconciled and convey mechanistic implications: The different models employed in these studies feature divergent anatomic and cellular compartmentalization of osteopontin expression and different osteopontin expression patterns by tumor cells.…”

Section: Discussionmentioning

confidence: 66%

“…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. Our data reconcile the results of previous studies on breast cancer, 15,46 and help explain the mononuclear chemoattractant function of tumor-originated osteopontin observed by others.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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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

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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“…The metastatic ability of tumor cells is increased with enhanced expression of OPN derived from the tumor cells or by stromal cells. Down-regulation of OPN expression and activity might provide novel strategies for the treatment of various types of metastatic cancer [45]. The local growth of OS involves bone destruction mediated by proteolytic and osteoclast activation.…”

Section: Osteopontin As a Target In Osteosarcoma Therapeuticsmentioning

confidence: 99%

Role of osteopontin in osteosarcoma

Deng

Zeng

et al. 2014

Med Oncol

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The primary bone malignancy osteosarcoma (OS) is a painful health burden, of which treatment remains a challenging problem. Identification of specific tumor biomarkers may help to investigate and develop the novel effective therapeutic approaches that have specific molecular target for the treatment of patients with OS. Osteopontin (OPN), a phosphorylated glycoprotein, is involved in many biological processes, such as biomineralization, bone remodeling and immune responses and has recently been reported to be associated with OS pathogenesis. Interestingly, both of the up- and down-regulation of OPN are involved in OS. During OS development, genetic or epigenetic disruption causes reduced expression of RUNX2 and OPN through the up-regulation of notch signaling pathway, leading to the development of OS. On the other hand, during hypoxic condition, upregulation of OPN induces the glucose uptake into hypoxic OS cells which is responsible for the OS cell proliferation and drug resistance. Recent evidences show that targeting OPN might be an important tool in OS therapeutics. This review has focused on the association of abnormal OPN expression with the pathogenesis of OS, the efficiency of OPN as a diagnostic tool for OS and the therapeutic aspects of OS by targeting OPN.

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“…Our data indicates that CD133 + subpopulation exhibits higher percentage of SP phenotypes which probably associated with chemoresistance against DTIC, Dox, Dabrafenib and Trametinib [7]. Osteopontin, a cytokine has multiple role in tumor progression and metastasis [10,11]. The study by Pietras et al have showed that osteopontin (OPN)-CD44 signaling axis in glioma niche enhances CSCs traits and promotes aggressive tumor growth [12].…”

Section: Commentarymentioning

confidence: 76%