The Potential of Osteopontin as a Therapeutic Target for Human Colorectal Cancer

Wang, Likui; Wang, Hong; Zhang, Shuwen; You, Yong; Wen, Yiping

doi:10.1007/s11605-011-1445-6

Cited by 24 publications

(24 citation statements)

References 28 publications

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“…We found that OPN, by binding to CD44, promotes tumorigenic properties, including enhanced clonogenicity and tumor growth in a xenograft model, similar to the previous study of OPN functions in colorectal cancer cell line (LoVo; ref. 37). In contrast, CD44-positive colorectal cancer cells promoted the secretion of OPN from macrophages in a CD44-dependent manner and, in a sense, "educated" the macrophages for their own benefit.…”

Section: Discussionmentioning

confidence: 98%

Reciprocal Interactions between Tumor-Associated Macrophages and CD44-Positive Cancer Cells via Osteopontin/CD44 Promote Tumorigenicity in Colorectal Cancer

Rao

Wang

et al. 2013

Clinical Cancer Research

114

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Purpose: CD44 is of functional importance for tumor initiation and progression in colorectal cancer, but how this molecule benefits cancer cells from the tumor microenvironment, especially tumor-associated macrophages (TAM), remains poorly defined.Experimental Design: In vivo tumorigenic assays were conducted to assess the role of murine TAMs in the tumorigenesis of human colorectal cancer cells. Both in vitro and in vivo osteopontin (OPN) expression levels in TAMs were examined by immunohistochemistry, quantitative PCR, and Western blotting. Soft agar colony formation assays were used to estimate the clonogenicity of colorectal cancer cells that had received different treatments. The relationships between the expression levels of OPN, CD44v6, and CD68 and clinical prognosis were evaluated by tissue microarray analysis.Results: We found that macrophages, when coinjected or cocultured with CD44-positive colorectal cancer cells, were able to produce higher levels of OPN, which in turn facilitated the tumorigenicity and clonogenicity of the colorectal cancer cells. The knockdown of CD44 or treatment with blocking antibodies to CD44 attenuated OPN secretion. OPN, through binding to its receptor CD44, activated c-jun-NH 2 -kinase signaling and promoted the clonogenicity of colorectal cancer cells. Moreover, tissue microarray data have shown that OPN expression, in combination with CD44v6, has a negative correlation with colorectal cancer patient survival.Conclusions: These results suggest that the OPN-CD44 interaction is important for colorectal cancer progression and could serve as a potential therapeutic target for the treatment of colorectal cancer. Clin Cancer Res; 19(4); 785-97. Ó2012 AACR.

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Section: Discussionmentioning

confidence: 98%

Reciprocal Interactions between Tumor-Associated Macrophages and CD44-Positive Cancer Cells via Osteopontin/CD44 Promote Tumorigenicity in Colorectal Cancer

Rao

Wang

et al. 2013

Clinical Cancer Research

114

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“…1) Annually, over 945000 people develop colorectal cancer, and about 492000 patients die from the disease.…”

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confidence: 99%

“…Therefore, there is an urgent need to develop new therapeutic targets and strategies, both of which can be realized through an increasing understanding of the molecular mechanisms governing colon progression. 1) AMP-activated protein kinase (AMPK) is a member of a family of serine-threonine protein kinases that are found in all eukaryotes. 4) AMPK is composed of three subunits (α, β, and γ).…”

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confidence: 99%

Magnolol-Induced Apoptosis in HCT-116 Colon Cancer Cells Is Associated with the AMP-Activated Protein Kinase Signaling Pathway

Park

Lee

Young

et al. 2012

Biological & Pharmaceutical Bulletin

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Colon cancer is the third most common malignancy around the world. Surgery, chemotherapy, and radiotherapy are generally used to treat colon cancer, but no effective therapy for advanced colon carcinoma is available. Therefore, there is a need to identify other therapeutic agents against this disease. Magnolol, a hydroxylated biphenyl compound present in Magnolia officinalis, exerts anticancer potential and low toxicity. Emerging evidence has suggested that activation of AMP-activated protein kinase (AMPK), a potential cancer therapeutic target is involved in apoptosis in colon cancer cells. However, the effects of magnolol on human colon cancer through activation of AMPK remain unexplored. In this study, we explored whether magnolol exerts an antiproliferative effect, and induces apoptosis in HCT-116 human colon cancer cells.

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“…In addition, a number of studies have demonstrated that OPN promoted tumor invasion and metastasis and regulated MMP-9 secretion (27)(28)(29)(30)(31). OPN was shown to combine with integrin αvβ3 and activate NF-κB (nuclear factor-κB) through the PI3K/Akt/IKK (κB kinase inhibitor) signaling pathway, increasing the secretion of urokinase-type plasmi nogen activator A (uPA) and promoting tumor invasion (32,33).…”

Section: Discussionmentioning

confidence: 99%

Role of osteopontin in the regulation of human bladder cancer proliferation and migration in T24 cells

Guo

Ding

et al. 2015

Molecular Medicine Reports

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Abstract. Osteopontin (OPN), a secreted acid glycoprotein with a variety of functions, promotes tumor proliferation, differentiation, invasion and metastasis. The aim of the current study was to investigate whether OPN may serve as a potential therapeutic target for human bladder cancer. RNA interference (RNAi) was performed to downregulate the expression of the OPN gene in T24 human bladder cancer cells. The mRNA and protein expression levels of OPN following RNAi were determined using reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. In addition, the cell cycle progression, apoptosis and proliferation were investigated using by flow cytometric analysis and MTT assay. The cell invasion ability was measured using a Matrigel transwell assay. The mRNA and protein expression levels of OPN were found to be significantly downregulated following RNAi. The proliferation and invasion of T24 cells were significantly inhibited in vitro. In conclusion, RNAi-targeting OPN may inhibit the proliferation, invasion and tumorigenicity of human bladder cancer cells. Therefore, OPN may serve as a potential therapeutic target for human bladder cancer. IntroductionBladder cancer is a common malignant tumors of the urinary system. In 2005, 63,210 new cases of bladder cancer were identified in America, of which 13,180 succumbed to the disease (1). With the development of an aging population, bladder cancer incidence is increasing year after year as incidence increases with age. Surgery is the main treatment method for bladder cancer; however, the 5-year average survival period remains poor (2). A previous study has demonstrated that the most important prognostic factors of bladder cancer include the pathological grading and staging (3). Long-term survival may be achieved through early detection and treatment. With the elucidation of the molecular biology of bladder cancer, gene therapy represents a novel method for the adjuvant treatment of the disease. Osteopontin (OPN) is a secreted acid glycoprotein with a variety of functions. OPN was initially isolated from the bone matrix and subsequently found in the tissues or cells of the placenta, decidua, smooth muscle and macrophages, as well as in various body fluids. In addition, OPN is an important component of the extracellular matrix. Previous studies have demonstrated that OPN is expressed in various tumor tissues and promotes tumor proliferation, differentiation, invasion and metastasis (4-9). A number of studies have shown that shorter survival time and poor prognosis are associated with high levels of OPN (10-13), while low plasma levels of OPN in patients are associated with good prognosis (14,15).RNA interference (RNAi) is a process of typical post-transcriptional regulation of gene expression, which is a conservative behavior in biological evolution, with resistance to virus invasion and maintaining the role of genetic stability (16,17,18). RNAi is induced by double-stranded RNA (dsRNA) gene silencing (18). When dsRNA is trans...

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The Potential of Osteopontin as a Therapeutic Target for Human Colorectal Cancer

Abstract: RNAi-targeting OPN could inhibit proliferation, invasion and enhance radiosensitivity of human CRC cells. Therefore, OPN could serve as a novel molecular target for gene therapy of CRC.

Cited by 24 publications

References 28 publications

Reciprocal Interactions between Tumor-Associated Macrophages and CD44-Positive Cancer Cells via Osteopontin/CD44 Promote Tumorigenicity in Colorectal Cancer

Reciprocal Interactions between Tumor-Associated Macrophages and CD44-Positive Cancer Cells via Osteopontin/CD44 Promote Tumorigenicity in Colorectal Cancer

Magnolol-Induced Apoptosis in HCT-116 Colon Cancer Cells Is Associated with the AMP-Activated Protein Kinase Signaling Pathway

Role of osteopontin in the regulation of human bladder cancer proliferation and migration in T24 cells

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