Metastatic suppressor CD44 is related with oxidative stress in breast cancer cell lines

Calaf, Gloria M.

doi:10.3892/ijo.2011.1154

Cited by 9 publications

(6 citation statements)

References 53 publications

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“…Although overexpression of CD44 correlates with bad prognosis in patients with most human cancers ( 151 , 178 – 184 ), it was also found that CD44 is extremely sensitive to changes in the microenvironment. For example, CD44 in breast cancer cells, neuroblastomas and prostate cancer may act as a metastatic suppressor gene ( 170 , 185 , 186 ), suggesting that the growth promoting pathways in these tumors are independent of CD44. These differential regulations should be considered carefully while designing CD44 as a target for therapeutic strategy.…”

Section: Discussionmentioning

confidence: 99%

“…CD44 is extremely sensitive to changes in the microenvironment. For example, CD44 in breast cancer cells may act as a metastatic suppressor gene when influenced by ROS, as seen by decreased CD44 protein expression in the malignant and tumorigenic breast cancer alpha 5 cell line in a compensatory response to increased manganese superoxide dismutase (MnSOD) protein expression ( 170 ). Studies by Stoop et al ( 171 ) showed that the cancer-initiating function in CD44-null mice was less severe, whereas the inflammatory functions were persistent in these mice suggesting again the possibility of a molecular redundancy in this model.…”

Section: Interaction Of Cd44 and Rhamm With Hamentioning

confidence: 99%

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Interactions between Hyaluronan and Its Receptors (CD44, RHAMM) Regulate the Activities of Inflammation and Cancer

et al. 2015

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The glycosaminoglycan hyaluronan (HA), a major component of extracellular matrices, and cell surface receptors of HA have been proposed to have pivotal roles in cell proliferation, migration, and invasion, which are necessary for inflammation and cancer progression. CD44 and receptor for HA-mediated motility (RHAMM) are the two main HA-receptors whose biological functions in human and murine inflammations and tumor cells have been investigated comprehensively. HA was initially considered to be only an inert component of connective tissues, but is now known as a “dynamic” molecule with a constant turnover in many tissues through rapid metabolism that involves HA molecules of various sizes: high molecular weight HA (HMW HA), low molecular weight HA, and oligosaccharides. The intracellular signaling pathways initiated by HA interactions with CD44 and RHAMM that lead to inflammatory and tumorigenic responses are complex. Interestingly, these molecules have dual functions in inflammations and tumorigenesis. For example, the presence of CD44 is involved in initiation of arthritis, while the absence of CD44 by genetic deletion in an arthritis mouse model increases rather than decreases disease severity. Similar dual functions of CD44 exist in initiation and progression of cancer. RHAMM overexpression is most commonly linked to cancer progression, whereas loss of RHAMM is associated with malignant peripheral nerve sheath tumor growth. HA may similarly perform dual functions. An abundance of HMW HA can promote malignant cell proliferation and development of cancer, whereas antagonists to HA-CD44 signaling inhibit tumor cell growth in vitro and in vivo by interfering with HMW HA-CD44 interaction. This review describes the roles of HA interactions with CD44 and RHAMM in inflammatory responses and tumor development/progression, and how therapeutic strategies that block these key inflammatory/tumorigenic processes may be developed in rodent and human diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Interaction Of Cd44 and Rhamm With Hamentioning

confidence: 99%

Interactions between Hyaluronan and Its Receptors (CD44, RHAMM) Regulate the Activities of Inflammation and Cancer

et al. 2015

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“…Elevated ROS generation is associated with alterations of metastatic genes in malignant breast cancer cell lines [41]. Previous studies show that ROS can activate downstream PI3K/AKT and ERK1/2 pathways that regulate HIF-1 and VEGF expression [42,43].…”

Section: Discussionmentioning

confidence: 99%

Deferoxamine Promotes MDA-MB-231 Cell Migration and Invasion through Increased ROS-Dependent HIF-1a Accumulation

Liu

Cui

Shi

et al. 2014

Cell Physiol Biochem

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Background/Aim: Deferoxamine (DFO), an iron chelator, has been reported to induce hypoxia-inducible factor-1α (HIF-1α) expression. HIF-1α plays a critical role in promoting tumor metastasis. However, the molecular mechanisms underlying induction of HIF-1α in breast cancer cells remain unknown. Our aim was to ascertain whether DFO enhanced cancer metastasis in MDA-MB-231 cells. Methods: Cellular reactive oxygen species (ROS) was measured by flow cytometry. Cell migration was determined by wound healing and transwell assays. Protein and mRNA expression were detected by western blotting and RT-PCR, respectively. Results: DFO treatment enhanced cell migration and invasion, while HIF-1α expression was significantly up-regulated at the post-transcriptional level. However, treatment with a NADPH oxidase inhibitor, diphenyleneiodonium (DPI), strongly inhibited ROS generation and HIF-1α expression, as well as cell migration and invasion. Notably, DFO treatment increased extracellular signal-regulated kinase (ERK)1/2 phosphorylation. Inhibition of ROS production with DPI attenuated DFO-induced ERK1/2 activation. Moreover, a MEK1 inhibitor, PD98059, suppressed DFO-induced cell migration and invasion. Conclusion: DFO-induced HIF-1α expression involves a cascade of signaling events including ROS generation, activation of ERK signaling, and subsequent promotion of cell migration and invasion. These findings indicate a risk associated with DFO and other iron chelators for treatment of tumors with invasive potential.

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“…Many cancer treatments including radiotherapy and chemotherapy regimens involve the generation of free radicals (e.g., hydroxyl radical, hydrogen peroxide, and superoxide anion) to induce oxidative stress to kill cancer cells [1, 2]. While oxidative stress mechanisms play a key role in cancer treatment, high levels of free radicals may negatively impact breast cancer prognosis through several mechanisms, including genomic instability potentially leading to treatment resistance, activation of cell signaling pathways involved in tumor cell proliferation, and increased tumor cell migration and pro-angiogenic factors [1, 3, 4]. We hypothesized that high systemic levels of oxidative stress after completion of chemotherapy and radiotherapy may negatively impact breast cancer prognosis.…”

Section: Introductionmentioning

confidence: 99%

Urinary biomarkers of oxidative stress and breast cancer survival

Nechuta

Cai

Zheng

et al. 2014

Cancer Causes Control

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PURPOSE Systemic oxidative stress has been implicated in the pathogenesis and progression of many chronic diseases, including breast cancer. No studies have investigated F2-isoprostanes (F2-IsoPs), valid biomarkers of systemic oxidative stress, in association with breast cancer prognosis. We conducted a nested case-control study in a prospective breast cancer survivor cohort to investigate systemic oxidative stress and survival. METHODS Urinary levels of F2-IsoPs and its major urinary metabolite (2,3-dinor-5,6-dihydro-15-F2t-IsoP, F2-IsoP-M) were measured post-cancer treatment using gas chromatography/negative ion chemical ionization mass spectrometry for 57 deceased breast cancer patients (cases) and 103 surviving patients (controls) matched 1:2 on age at diagnosis, stage, and diagnosis year. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from conditional logistic regression models. RESULTS In unadjusted models, elevated F2-IsoP levels categorized based on the median value (≥1.73;<1.73 (reference)) were non-significantly inversely associated with mortality (OR:0.51, 95% CI:0.24–1.10). After adjustment for potential confounders, elevated F2-IsoP levels were significantly associated with mortality (OR:0.36, 95% CI:0.14–0.96). The inverse association was marginally significant when F2-IsoP was categorized based on tertiles (Ptrend=0.08). In contrast, elevated F2-IsoP-M levels, categorized based on the median level (≥0.91;<0.91(reference)), were associated with a statistically non-significant increased risk of mortality in both unadjusted and adjusted models (adjusted OR:1.39, 95% CI:0.62–3.09). CONCLUSION Results suggest a role for oxidative stress biomarkers in breast cancer survival; however, as this is the first study to date, additional larger studies are needed.

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Metastatic suppressor CD44 is related with oxidative stress in breast cancer cell lines

Cited by 9 publications

References 53 publications

Interactions between Hyaluronan and Its Receptors (CD44, RHAMM) Regulate the Activities of Inflammation and Cancer

Interactions between Hyaluronan and Its Receptors (CD44, RHAMM) Regulate the Activities of Inflammation and Cancer

Deferoxamine Promotes MDA-MB-231 Cell Migration and Invasion through Increased ROS-Dependent HIF-1a Accumulation

Urinary biomarkers of oxidative stress and breast cancer survival

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