Categorical meta-analysis of Osteopontin as a clinical cancer marker

Wéber,

doi:10.3892/or.2010.1106

Cited by 62 publications

(54 citation statements)

References 26 publications

(40 reference statements)

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“…Notably, although the link between overexpression of osteopontin and worse outcome is clear, meta-analysis of osteopontin in breast cancer concluded that osteopontin expression is independent of breast cancer subtypes (42). However, the role of tumor-derived osteopontin in modulating the tumor microenvironment is largely unresolved.…”

Section: Discussionmentioning

confidence: 99%

Tumor-Derived Osteopontin Reprograms Normal Mammary Fibroblasts to Promote Inflammation and Tumor Growth in Breast Cancer

et al. 2015

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Breast tumors are characterized by an extensive desmoplastic stroma, abundantly populated by fibroblasts. Cancer-associated fibroblasts (CAF) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation, and invasion. CAF also orchestrate tumor-promoting inflammation in multiple tumor types, including breast cancer. However, the mechanisms through which normal tissue fibroblasts are reprogrammed to tumor-promoting CAFs are mainly obscure. Here, we show that mammary fibroblasts can be educated by breast cancer cells to become activated to a proinflammatory state that supports malignant progression. Proteomic analysis of breast cancer cell-secreted factors identified the secreted proinflammatory mediator osteopontin, which has been implicated in inflammation, tumor progression, and metastasis. Osteopontin was highly secreted by mouse and human breast cancer cells, and tumor cell-secreted osteopontin activated a CAF phenotypes in normal mammary fibroblasts in vitro and in vivo. Osteopontin was sufficient to induce fibroblast reprogramming and neutralizing antibodies against osteopontinblocked fibroblast activation induced by tumor cells. The ability of secreted osteopontin to activate mammary fibroblasts relied upon its known receptors CD44 and a V b 3 integrin. Strikingly, osteopontin silencing in tumor cells in vivo attenuated stromal activation and inhibited tumor growth. Our findings establish a critical functional role for paracrine signaling by tumor-derived osteopontin in reprograming normal fibroblasts into tumor-promoting CAFs. Cancer Res; 75(6); 963-73. Ó2015 AACR.

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Section: Discussionmentioning

confidence: 99%

Tumor-Derived Osteopontin Reprograms Normal Mammary Fibroblasts to Promote Inflammation and Tumor Growth in Breast Cancer

et al. 2015

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“…Osteopontin expression has been associated with breast cancer progression, regardless of the histologic subtype of the cancer (4,6). Importantly, the polymorphic site at -443, but not -1748 or -1776, showed differences between ER-positive and ER-negative breast cancers and between PR-positive and PR-negative breast cancers, but there was no association with HER2 status.…”

Section: Resultsmentioning

confidence: 91%

“…Osteopontin is a metastasis-related gene that contributes to the progression of over 30 forms of cancer (3)(4)(5). Aberrant splicing of osteopontin in cancers has been accounted for by our identification of the variant form osteopontin-c, which is selectively expressed in cancer cells but is absent from non-transformed cells (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

An osteopontin promoter polymorphism is associated with aggressiveness in breast cancer

Ramchandani

Weber

2013

Oncology Reports

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Abstract. Metastasis-related genes are deregulated in cancer by aberrant expression or splicing. Here, we analyzed polymorphic sites in the osteopontin promoter as potential contributors to aberrant expression in breast cancers. This study comprised 241 breast cancer specimens, for which DNA from normal surrounding tissue was available for 111, and 65 healthy breast samples. The polymorphic site in position -443 of the promoter was associated with tumor grade. As expected, there was no association between promoter single nucleotide polymorphisms (SNPs) and tumor stage or in situ carcinoma versus cancer, as stage and early transformation are determined by the sampling time more than by tumor genetics. In a subset of samples, osteopontin RNA expression levels had previously been obtained. The allelic distribution in positions -443 and -1748 was distinct between high and low expressors, confirming the importance of promoter SNPs. These two sites also form a haplotype. Osteopontin expression has been associated with breast cancer progression, regardless of the histological subtype of the cancer. Remarkably, the polymorphic site at -443, but not -1748 or -1776, showed differences between ER-positive and ER-negative breast cancers and between PR-positive and PR-negative breast cancers, but there was no association with HER2 status. In five cases, the genotype of the tumor was different from the genotype of the host, implying the possibility of somatic mutations in the osteopontin promoter that may affect expression. Our results corroborate that the osteopontin promoter SNPs -443 (rs11730582) and -1748 (rs2728127) are important for gene expression and breast cancer aggressiveness.

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“…As a multi-functional cytokine, OPN is involved in cell survival, migration and adhesion which is associated with tumorigenesis, progression and metastasis. OPN is also implicated in tumorgenesis and has been proposed as a cancer marker including nasopharyngeal carcinoma, lung cancer, colon cancer and prostate cancer [10,11]. …”

Section: Introductionmentioning

confidence: 99%

The OPN Gene Polymorphism Confers the Susceptibility and Response to Ara-C Based Chemotherapy in Chinese AML Patients

Zhang¹,

Yang²,

Li³

et al. 2015

Cell Physiol Biochem

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Aim: To investigate the possible association between the Osteopontin (OPN) gene polymorphisms and the susceptibility and chemotherapy response of acute myeloid leukemia patients. Methods: A total of 381 patients with de nova AML and 430 healthy controls were enrolled. All patients received Ara-C-based standard induction chemotherapy regimens, and the treatment response was evaluated. Several polymorphisms in the human OPN encoding gene have been identified. The OPN) gene polymorphisms at 3 loci, namely, -156 GG>G, -443 C>T and -66T>G were determined. Results: We identified that the -443C>T polymorphism was the only one which is closely related to AML. Compared with the -443TT carriers, our data showed that the -443CC genotype carriers were significantly related to a higher risk for AML. The -443CC genotype was also more prevalent in poor response groups than in good response group. The -443CC carriers are more likely to have poor response to AML treatment. Cellular assay indicated that the leukemic cell lines receiving the OPN -443C transfection have a significantly lower apoptosis rate to Ara-C treatment compared to cell lines transfected with -443T. Conclusion: The findings of this study suggest OPN-443C>T gene polymorphism may be sued as a molecular for susceptibility and chemotherapy response of AML.

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Categorical meta-analysis of Osteopontin as a clinical cancer marker

Cited by 62 publications

References 26 publications

Tumor-Derived Osteopontin Reprograms Normal Mammary Fibroblasts to Promote Inflammation and Tumor Growth in Breast Cancer

Tumor-Derived Osteopontin Reprograms Normal Mammary Fibroblasts to Promote Inflammation and Tumor Growth in Breast Cancer

An osteopontin promoter polymorphism is associated with aggressiveness in breast cancer

The OPN Gene Polymorphism Confers the Susceptibility and Response to Ara-C Based Chemotherapy in Chinese AML Patients

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