Glycoprotein Nonmetastatic B Is an Independent Prognostic Indicator of Recurrence and a Novel Therapeutic Target in Breast Cancer

Rose, April A.N.; Grosset, Andrée-Anne; Dong, Zhifeng; Russo, Caterina; MacDonald, Penny A.; Bertos, Nicholas; St‐Pierre, Yves; Simantov, Ronit; Hallett, Michael; Park, Morag; Gaboury, Louis; Siegel, Peter M.

doi:10.1158/1078-0432.ccr-09-1611

Cited by 167 publications

(167 citation statements)

References 36 publications

(50 reference statements)

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“…GPNMB is involved in several diseases. Higher expression of the GPNMB gene was found in tumor cells for different cancers, including glioma and melanoma [15,16], glioblastoma multiforme [9] and breast cancer [17], and overexpression of GPNMB was shown to decrease tumor growth [18]. GPNMB is considered to be a potential target for the treatment of malignancies.…”

Section: Neurochem Resmentioning

confidence: 99%

MiR-508-5p Inhibits the Progression of Glioma by Targeting Glycoprotein Non-metastatic Melanoma B

Bao

Wang

et al. 2016

Neurochem Res

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Glioma is a severe and highly lethal brain cancer, a malignancy largely stemming from growing in a relatively restrained area of the brain. Hence, the understanding of the molecular regulation of the growth of glioma is critical for improving its treatment. MicroRNA has become a hotspot in research on diseases, especially in the initiation and progression of different types of cancer. However, the molecular function and mechanisms of miR-508-5p in gliomagenesis are still unclear. The aim of this study was to investigate miR-508-5p expression in glioma and determine its effects on proliferation. miR-508-5p expression levels, both in glioma cell lines and in tissue, were significantly lower than in a normal human astrocyte cell line or adjacent tissues. Cell growth was analyzed using a MTT assay and over-expression of miR-508-5p was found to decrease glioma cell growth. Moreover, a bioinformatic analysis was performed, showing that glycoprotein non-metastatic melanoma B (GPNMB) was a direct target for miR-508-5p in glioma cells. Furthermore, in vivo treatment with miR-508-5p reduced GPNMB protein levels in the tumor. Additionally, overexpression of GPNMB without 3'-UTR partially reversed the cell growth arrest induced by miR-508-5p over-expression in glioma cells. In conclusion, these results indicate that increased expression of miR-508-5p might be related to glioma progression, indicating a potential role of miR-508-5p for clinical therapy.

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Section: Neurochem Resmentioning

confidence: 99%

MiR-508-5p Inhibits the Progression of Glioma by Targeting Glycoprotein Non-metastatic Melanoma B

Bao

Wang

et al. 2016

Neurochem Res

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“…Then, they employed IHC-based analysis of tissue microarrays to investigate the relevance of Gpnmb/OA expression in human breast cancer, and found that Gpnmb/OA was expressed in the tumor epithelium of approximately 10% of human breast cancers and the stromal compartment of nearly 70% of breast tumors. Moreover, epithelial, but not stromal, Gpnmb/OA expression was a prognostic indicator of cancer recurrence across all breast cancer subtypes, and specifically within "triple negative" breast cancers [24].…”

mentioning

confidence: 94%

“…In addition to its diverse roles in normal cells, aberrant Gpnmb/OA expression had been linked to various pathological disorders such as glaucoma [18], kidney disease [19][20][21] and osteoarthritis [22]. Gpnmb/OA was also expressed at higher levels in several malignant human tissues, such as hepatocellular carcinoma [7], glioma [4,5], melanoma [1,23] and breast cancer cells [6,24], relative to corresponding normal tissue.…”

mentioning

confidence: 99%

Gpnmb/osteoactivin, an attractive target in cancer immunotherapy

Zhou¹,

Liu²,

Li³

et al. 2012

neo

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Cancer is a complex disease with interactions between normal and neoplastic cells. Since current therapies for cancer largely rely on drugs or radiation that kill dividing cells or block cell division, these treatments may have severe side effects on normal proliferating cells in patients with cancer. Recently, immunotherapeutic approaches for cancer therapy, by which monoclonal antibodies (Mabs) target tumor specific antigens, have shown great potential. Glycoprotein non-metastatic melanoma protein B (Gpnmb)/Osteoactivin (OA) is a transmembrane glycoprotein highly expressed in various types of cancer. Gpnmb/OA promotes the migration, invasion and metastasis of tumor cells. CR 011-vcMMAE is a Mab-drug conjugate being developed for the treatment of Gpnmb/OA-expressing cancers. Gpnmb/OA represents an attractive target in cancer immunotherapy and CR011-vcMMAE holds promise as a reagent in targeted therapy for Gpnmb/OA-expressing malignancies.

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“…22 Using this system, we identified targets relevant to breast cancer progression and bone metastasis. 22,23 We now describe the identification of three members of the CCN family as differentially expressed in weakly versus aggressively bone metastatic breast cancer cells. The present results indicate that CCN3 functions to promote the formation of osteolytic breast cancer metastases by modulating the bone microenvironment to favor osteoclast differentiation.…”

mentioning

confidence: 99%

CCN3 Impairs Osteoblast and Stimulates Osteoclast Differentiation to Favor Breast Cancer Metastasis to Bone

Ouellet

Tiedemann

Mourskaia

et al. 2011

The American Journal of Pathology

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Bone is a preferred site for breast cancer metastasis, causing pain, fractures, spinal cord compressions, and hypercalcemia, all of which can significantly diminish the patient's quality of life. We identified CCN3 as a novel factor that is highly expressed in bone metastatic breast cancer cells from a xenograft mouse model and in bone metastatic lesions from patients with breast cancer. We demonstrate that CCN3 overexpression enhances the ability of weakly bone metastatic breast cancer cells to colonize and grow in the bone without altering their growth in the mammary fat pad. We further demonstrated that human recombinant CCN3 inhibits osteoblast differentiation from primary bone marrow cultures, leading to a higher receptor activator of NF-B ligand (RANKL)/osteoprotegerin (OPG) ratio. In conjunction with its ability to impair osteoblast differentiation, we uncovered a novel role for CCN3 in promoting osteoclast differentiation from RANKL-primed monocyte precursors. CCN3 exerts its proosteoclastogenic effects by promoting calcium oscillations and nuclear factor of activated T cells c1 (NFATc1) nuclear translocation. Together, these results demonstrate that CCN3 regulates the differentiation of bone resident cells to create a resorptive environment that promotes the formation of osteolytic breast cancer metastases. Bone is the preferred site for breast cancer metastasis. 1,2Although patients with bone metastasis display better overall survival relative to patients with visceral metastases, their quality of life can be significantly diminished due to pain, fractures, spinal cord compressions, and hypercalcemia. Given the pivotal role of the osteoclast in bone breakdown associated with osteolytic lesions, bisphosphonates (a class of drugs that inhibit osteoclast-dependent bone resorption) are routinely given to patients with breast cancer bone metastases. 4 However, significant research efforts are now focused on the identification and development of targeted therapeutics to further enhance the management of breast cancer metastasis. 5,6

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Glycoprotein Nonmetastatic B Is an Independent Prognostic Indicator of Recurrence and a Novel Therapeutic Target in Breast Cancer

Cited by 167 publications

References 36 publications

MiR-508-5p Inhibits the Progression of Glioma by Targeting Glycoprotein Non-metastatic Melanoma B

MiR-508-5p Inhibits the Progression of Glioma by Targeting Glycoprotein Non-metastatic Melanoma B

Gpnmb/osteoactivin, an attractive target in cancer immunotherapy

CCN3 Impairs Osteoblast and Stimulates Osteoclast Differentiation to Favor Breast Cancer Metastasis to Bone

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