High expression of leptin receptor leads to temozolomide resistance with exhibiting stem/progenitor cell features in gliobalastoma

Han, Gangwen; wang, laixing; Zhao, Wenyuan; Yue, Zhijian; Zhao, Rui; li, yanan; Zhou, Xiao‐Ping; Xiao-hu, HU; Liu, Jianmin

doi:10.4161/cc.26809

Cited by 21 publications

(26 citation statements)

References 39 publications

(37 reference statements)

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“…Indeed, obese mice treated with Doxorubicin showed more proliferative tumors that also had more CSC as compared with non-obese mice[164]. Leptin increases the expression of ABC protein transporters in glioblastoma[165]. Our preliminary data further show that leptin increases the expression of ABCB1 in breast and pancreatic cancer cells.…”

Section: Obesity Leptin and Drug Resistancementioning

confidence: 63%

Leptin signaling and cancer chemoresistance: Perspectives

Candelaria¹,

Rampoldi²,

Harbuzariu³

et al. 2017

WJCO

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Obesity is a major health problem and currently is endemic around the world. Obesity is a risk factor for several different types of cancer, significantly promoting cancer incidence, progression, poor prognosis and resistance to anti-cancer therapies. The study of this resistance is critical as development of chemoresistance is a serious drawback for the successful and effective drug-based treatments of cancer. There is increasing evidence that augmented adiposity can impact on chemotherapeutic treatment of cancer and the development of resistance to these treatments, particularly through one of its signature mediators, the adipokine leptin. Leptin is a pro-inflammatory, pro-angiogenic and pro-tumorigenic adipokine that has been implicated in many cancers promoting processes such as angiogenesis, metastasis, tumorigenesis and survival/resistance to apoptosis. Several possible mechanisms that could potentially be developed by cancer cells to elicit drug resistance have been suggested in the literature. Here, we summarize and discuss the current state of the literature on the role of obesity and leptin on chemoresistance, particularly as it relates to breast and pancreatic cancers. We focus on the role of leptin and its significance in possibly driving these proposed chemoresistance mechanisms, and examine its effects on cancer cell survival signals and expansion of the cancer stem cell sub-populations.

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Section: Obesity Leptin and Drug Resistancementioning

confidence: 63%

Leptin signaling and cancer chemoresistance: Perspectives

Candelaria¹,

Rampoldi²,

Harbuzariu³

et al. 2017

WJCO

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“…This signaling pathway is thought to play a role in self-renewal in leptin receptor-positive cells and TMZ resistance. Significant expression of the leptin receptor has been shown in CD133+ cells and knockdown of leptin receptor effectively lowered the invasiveness of stem-like cells in gliomas and confirmed that JAK/STAT3 signaling is the molecular mechanism involved in the invasion of U87 glioma cells (Han et al, 2013). Another study suggests ObR as an important target for anti-cancer therapy as the ObR+ glioblastoma cells possessing glioblastoma stem cell properties were associated with vasculogenic mimicry formation and microvascular density (MVD) (Han et al, 2017).…”

Section: Discussionmentioning

confidence: 86%

“…However, except in a few cancer types, such as breast, prostate, and colorectal cancers, the role of leptin in other tumors, such as lung (Unsal et al, 2014) and liver (Saxena et al, 2007) cancer is controversial and warrants further studies to provide a conclusive result. In addition, information on leptin in CNS tumors is limited and very few studies that explain this association exist (Yeh et al, 2009;Han et al, 2014;Riolfi et al, 2010;Ferla et al, 2011;Han et al, 2013;Russo et al, 2004).…”

Section: The Expression Of Leptin and Its Receptor During Tumorigenesmentioning

confidence: 99%

The Expression of Leptin and Its Receptor During Tumorigenesis of Diffuse Gliomas such as Astrocytoma and Oligodendroglioma - Grade II, III and IV (NOS)

Vokuda

Srinivas

Madhugiri

et al. 2019

Asian Pac J Cancer Prev

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Background:Leptin, an adipocytokine functions via the leptin receptor, OB-Rb that contains an intact intracellular domain and activates the JAK/STAT signalling cascade. It stimulates growth, migration and invasion of cancer cells in vitro potentiating angiogenesis. Recently, the involvement of leptin in tumor progression is being explored. Gliomas exhibit poor prognosis, low survival rates demanding for novel therapeutic regimens resulting in discovery of many potential biomarkers and pharmaceutical targets. We analysed the potential role of leptin and OB-Rb in carcinogenesis of malignant gliomas. Methods:Sixty fresh tissue samples of diffuse gliomas were collected after tumor excision. Real time PCR, immunohistochemical (IHC) analysis and western blot analysis were carried out to assess the expression of leptin and its receptor. Results:The present study demonstrates the expression of leptin and LepR and their involvement in tumor progression. Of the 60 cases, 57 cases (95%) and 53 cases (88.3%) showed amplification for leptin and OB-Rb respectively. The expression of these proteins were measured semi-quantitatively and correlated with degree of malignancy (p<0.05). The bands were visualised on western blot. Conclusion:Leptin may be valued as a pharmaceutical target and anti-leptin compounds could be developed as drugs in mono- or combined therapies for these tumors.

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“…Indeed, ObR was found expressed in CD133 + glioma CSCs, which underwent increase of invasive capacities in presence of leptin in vitro; this indicates that leptin might be a key intermediary player between excessive adipokine accumulation/obesity and CSC invasiveness/glioma formation [182]. Another study confirmed these findings and showed that ObR + glioblastoma stem/progenitor cells, via STAT3-mediated SOX2/OCT4 signaling, resulted resistant to temozolomide [183].…”

Section: Role Of Leptinmentioning

confidence: 81%

“…Amongst hormones, imbalanced leptin levels seem to be correlated to maintenance of pluripotency in CSCs [178], stimulating breast CSC growth [179,180], colorectal CSC proliferation [181] and glioma CSC invasiveness [182,183]. Additionally, high consumption of dairy products seems to increase IGF-1 level, implicated in prostate cancer risk [167,169], colon CSC proliferation [171], colon CSC chemoresistance [172] and acquisition of a glioma CSC malignant phenotype [173] (Figure 2).…”

Section: Discussionmentioning

confidence: 92%

Role of Environmental Chemicals, Processed Food Derivatives, and Nutrients in the Induction of Carcinogenesis

Persano

Zagoura

Louisse

et al. 2015

Stem Cells and Development

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In recent years it has been hypothesized that cancer stem cells (CSCs) are the actual driving force of tumor formation, highlighting the need to specifically target CSCs to successfully eradicate cancer growth and recurrence. Particularly, the deregulation of physiological signaling pathways controlling stem cell proliferation, self-renewal, differentiation, and metabolism is currently considered as one of the leading determinants of cancer formation. Given their peculiar, slow-dividing phenotype and their ability to respond to multiple microenvironmental stimuli, stem cells appear to be more susceptible to genetic and epigenetic carcinogens, possibly undergoing mutations resulting in tumor formation. In particular, some animal-derived bioactive nutrients and metabolites known to affect the hormonal milieu, and also chemicals derived from food processing and cooking, have been described as possible carcinogenic factors. Here, we review most recent literature in this field, highlighting how some environmental toxicants, some specific nutrients and their secondary products can induce carcinogenesis, possibly impacting stem cells and their niches, thus causing tumor growth.

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High expression of leptin receptor leads to temozolomide resistance with exhibiting stem/progenitor cell features in gliobalastoma

Cited by 21 publications

References 39 publications

Leptin signaling and cancer chemoresistance: Perspectives

Leptin signaling and cancer chemoresistance: Perspectives

The Expression of Leptin and Its Receptor During Tumorigenesis of Diffuse Gliomas such as Astrocytoma and Oligodendroglioma - Grade II, III and IV (NOS)

Role of Environmental Chemicals, Processed Food Derivatives, and Nutrients in the Induction of Carcinogenesis

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