Stem Cells in Tumour Microenvironment Aid in Prolonged Survival Rate of Cancer Cells and Developed Drug Resistance: Major Challenge in Osteosarcoma Treatment

2020 ◽  
Vol 21 (1) ◽  
pp. 44-52
Author(s):  
Bhaskar Birru ◽  
ChandraSai Potla Durthi ◽  
Santhosh Kacham ◽  
Madhuri Pola ◽  
Satish Babu Rajulapati ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Tumour Progression ◽  
Combined Treatment ◽  
Bone Cancer ◽  
Tumour Microenvironment ◽  
Surgical Removal ◽  
Therapeutic Approaches ◽  
Hypoxic Environment

Osteosarcoma is an aggressive bone cancer found in children and adolescents. The combined treatment strategy includes the surgical removal of tumour and subsequent chemotherapy to prevent the reoccurrence has been a widely accepted approach. However, the drug resistance developed by tumour cells causes recurrence of cancer. It is imperative to understand the molecular mechanism involved in the development of drug resistance and tumour progression for developing potential therapy. Tumour microenvironment and cellular cross-talk via activation of various signalling pathways are responsible for tumour progression and metastasis. The comprehensive reviews are already available on the tumour microenvironment, signalling cascades responsible for tumour progression, and cellular crosstalk between malignant cells and immune cells. Therefore, we intend to provide comprehend review postulating the importance of mesenchymal stem cells (MSCs) in osteosarcoma progression and metastasis. This paper is aimed to provide information sequentially includes: tumour microenvironment, MSCs role in osteosarcoma progression, the hypoxic environment in MSCs recruitment at the tumour site and the importance of exosomes in tumorigenesis, progression and metastasis. Overall, this review may enlighten the research on the role of MSCs and MSCs derived exosome in osteosarcoma progression and drug resistance. This possibly may result in developing novel therapeutic approaches to combat the osteosarcoma effectively and contributes for the development of prognosis tools for early diagnosis.

scholarly journals The role of mesenchymal stem cells in anti-cancer drug resistance and tumour progression

2012 ◽  
Vol 106 (12) ◽  
pp. 1901-1906 ◽  
Author(s):  
J M Houthuijzen ◽  
L G M Daenen ◽  
J M L Roodhart ◽  
E E Voest
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Mesenchymal Stem Cells ◽  
Tumour Progression ◽  
Cancer Drug ◽  
Cancer Drug Resistance ◽  
Anti Cancer

scholarly journals The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1239
Author(s):  
Leila Jahangiri ◽  
Tala Ishola ◽  
Perla Pucci ◽  
Ricky M. Trigg ◽  
Joao Pereira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Regulatory Networks ◽  
Epithelial To Mesenchymal Transition ◽  
Tumour Microenvironment ◽  
Repair Capacity ◽  
Mesenchymal Transition ◽  
Cellular Processes

Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways.

scholarly journals Targeting Protein Kinase C in Glioblastoma Treatment

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 381
Author(s):  
Noelia Geribaldi-Doldán ◽  
Irati Hervás-Corpión ◽  
Ricardo Gómez-Oliva ◽  
Samuel Domínguez-García ◽  
Félix A. Ruiz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Combined Treatment ◽  
Primary Brain Tumor ◽  
Kinase C ◽  
Pkc Isozymes ◽  
New Generation ◽  
Effective Drugs

Glioblastoma (GBM) is the most frequent and aggressive primary brain tumor and is associated with a poor prognosis. Despite the use of combined treatment approaches, recurrence is almost inevitable and survival longer than 14 or 15 months after diagnosis is low. It is therefore necessary to identify new therapeutic targets to fight GBM progression and recurrence. Some publications have pointed out the role of glioma stem cells (GSCs) as the origin of GBM. These cells, with characteristics of neural stem cells (NSC) present in physiological neurogenic niches, have been proposed as being responsible for the high resistance of GBM to current treatments such as temozolomide (TMZ). The protein Kinase C (PKC) family members play an essential role in transducing signals related with cell cycle entrance, differentiation and apoptosis in NSC and participate in distinct signaling cascades that determine NSC and GSC dynamics. Thus, PKC could be a suitable druggable target to treat recurrent GBM. Clinical trials have tested the efficacy of PKCβ inhibitors, and preclinical studies have focused on other PKC isozymes. Here, we discuss the idea that other PKC isozymes may also be involved in GBM progression and that the development of a new generation of effective drugs should consider the balance between the activation of different PKC subtypes.

scholarly journals The Duality of Caspases in Cancer, as Told through the Fly

2021 ◽  
Vol 22 (16) ◽  
pp. 8927
Author(s):  
Caitlin Hounsell ◽  
Yun Fan
Keyword(s):  
Tumour Progression ◽  
Critical Role ◽  
Dual Role ◽  
Activity Level ◽  
Therapeutic Approaches ◽  
Cancer Treatments ◽  
Aspartic Proteases ◽  
Critical Components ◽  
Established Role

Caspases, a family of cysteine-aspartic proteases, have an established role as critical components in the activation and initiation of apoptosis. Alongside this a variety of non-apoptotic caspase functions in proliferation, differentiation, cellular plasticity and cell migration have been reported. The activity level and context are important factors in determining caspase function. As a consequence of their critical role in apoptosis and beyond, caspases are uniquely situated to have pathological roles, including in cancer. Altered caspase function is a common trait in a variety of cancers, with apoptotic evasion defined as a “hallmark of cancer”. However, the role that caspases play in cancer is much more complex, acting both to prevent and to promote tumourigenesis. This review focuses on the major findings in Drosophila on the dual role of caspases in tumourigenesis. This has major implications for cancer treatments, including chemotherapy and radiotherapy, with the activation of apoptosis being the end goal. However, such treatments may inadvertently have adverse effects on promoting tumour progression and acerbating the cancer. A comprehensive understanding of the dual role of caspases will aid in the development of successful cancer therapeutic approaches.

scholarly journals Hypoxia and proangiogenic proteins in human ameloblastoma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Raíssa Pinheiro de Mendonça ◽  
Karolyny Martins Balbinot ◽  
Beatriz Voss Martins ◽  
Maria Sueli da Silva Kataoka ◽  
Ricardo Alves Mesquita ◽  
...  
Keyword(s):  
Aggressive Behaviour ◽  
Tumour Progression ◽  
Tumour Microenvironment ◽  
Odontogenic Cysts ◽  
Biological Behaviour ◽  
Odontogenic Tumours ◽  
Anti Vegf ◽  
The Mean

Abstract Ameloblastomas are epithelial odontogenic tumours that, although benign, are locally invasive and may exhibit aggressive behaviour. In the tumour microenvironment, the concentration of oxygen is reduced, which leads to intratumoral hypoxia. Under hypoxia, the crosstalk between the HIF-1α, MMP-2, VEGF, and VEGFR-2 proteins has been associated with hypoxia-induced angiogenesis, leading to tumour progression and increased invasiveness. This work showcases 24 ameloblastoma cases, 10 calcifying odontogenic cysts, and 9 dental follicles, used to investigate the expression of these proteins by immunohistochemistry. The anti-HIF-1α, anti-MMP-2, anti-VEGF, and anti-VEGFR-2 primary antibodies are used in this work. The results have been expressed by the mean grey value after immunostaining in images acquired with an objective of 40×. The ameloblastoma samples showed higher immunoexpression of HIF-1α, MMP-2, VEGF, and VEGFR-2 when compared to the dental follicles and calcifying odontogenic cysts. Ameloblastomas show a higher degree of expression of proteins associated with intratumoral hypoxia and proangiogenic proteins, which indicates the possible role of these proteins in the biological behaviour of this tumour.

scholarly journals Normoxic Tumour Extracellular Vesicles Modulate the Response of Hypoxic Cancer and Stromal Cells to Doxorubicin In Vitro

2020 ◽  
Vol 21 (17) ◽  
pp. 5951
Author(s):  
Laura Patras ◽  
Marcel H. A. M. Fens ◽  
Pieter Vader ◽  
Arjan Barendrecht ◽  
Alina Sesarman ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Extracellular Vesicles ◽  
Hypoxia Inducible Factor ◽  
B Cell Lymphoma ◽  
Tumour Microenvironment ◽  
Hypoxia Inducible Factor 1 ◽  
Apoptotic Protein ◽  
Donor Cells

Extracellular vesicles (EV) secreted in the tumour microenvironment (TME) are emerging as major antagonists of anticancer therapies by orchestrating the therapeutic outcome through altering the behaviour of recipient cells. Recent evidence suggested that chemotherapeutic drugs could be responsible for the EV-mediated tumour–stroma crosstalk associated with cancer cell drug resistance. Here, we investigated the capacity of tumour EV (TEV) secreted by normoxic and hypoxic (1% oxygen) C26 cancer cells after doxorubicin (DOX) treatment to alter the response of naïve C26 cells and RAW 264.7 macrophages to DOX. We observed that C26 cells were less responsive to DOX treatment under normoxia compared to hypoxia, and a minimally cytotoxic DOX concentration that mounted distinct effects on cell viability was selected for TEV harvesting. Homotypic and heterotypic pretreatment of naïve hypoxic cancer and macrophage-like cells with normoxic DOX-elicited TEV rendered these cells slightly less responsive to DOX treatment. The observed effects were associated with strong hypoxia-inducible factor 1-alpha (HIF-1α) induction and B-cell lymphoma–extra-large anti-apoptotic protein (Bcl-xL)-mediated anti-apoptotic response in normoxic DOX-treated TEV donor cells, being also tightly connected to the DOX-TEV-mediated HIF-1α induction, as well as Bcl-xL levels increasing in recipient cells. Altogether, our results could open new perspectives for investigating the role of chemotherapy-elicited TEV in the colorectal cancer TME and their modulatory actions on promoting drug resistance.

scholarly journals Vitamin D-Induced Molecular Mechanisms to Potentiate Cancer Therapy and to Reverse Drug-Resistance in Cancer Cells

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1798 ◽  
Author(s):  
Mariarosaria Negri ◽  
Annalisa Gentile ◽  
Cristina de Angelis ◽  
Tatiana Montò ◽  
Roberta Patalano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Vitamin D ◽  
Drug Resistance ◽  
Cancer Therapy ◽  
Cancer Stem Cells ◽  
Crucial Role ◽  
Molecular Mechanisms ◽  
Vitamin D Supplementation

Increasing interest in studying the role of vitamin D in cancer has been provided by the scientific literature during the last years, although mixed results have been reported. Vitamin D deficiency has been largely associated with various types of solid and non-solid human cancers, and the almost ubiquitous expression of vitamin D receptor (VDR) has always led to suppose a crucial role of vitamin D in cancer. However, the association between vitamin D levels and the risk of solid cancers, such as colorectal, prostate and breast cancer, shows several conflicting results that raise questions about the use of vitamin D supplements in cancer patients. Moreover, studies on vitamin D supplementation do not always show improvements in tumor progression and mortality risk, particularly for prostate and breast cancer. Conversely, several molecular studies are in agreement about the role of vitamin D in inhibiting tumor cell proliferation, growth and invasiveness, cell cycle arrest and inflammatory signaling, through which vitamin D may also regulate cancer microenvironment through the activation of different molecular pathways. More recently, a role in the regulation of cancer stem cells proliferation and short non-coding microRNA (miRNAs) expression has emerged, conferring to vitamin D a more crucial role in cancer development and progression. Interestingly, it has been shown that vitamin D is able not only to potentiate the effects of traditional cancer therapy but can even contribute to overcome the molecular mechanisms of drug resistance—often triggering tumor-spreading. At this regard, vitamin D can act at various levels through the regulation of growth of cancer stem cells and the epithelial–mesenchymal transition (EMT), as well as through the modulation of miRNA gene expression. The current review reconsiders epidemiological and molecular literature concerning the role of vitamin D in cancer risk and tumor development and progression, as well as the action of vitamin D supplementation in potentiating the effects of drug therapy and overcoming the mechanisms of resistance often triggered during cancer therapies, by critically addressing strengths and weaknesses of available data from 2010 to 2020.

scholarly journals Crucial role of HMGA1 in the self-renewal and drug resistance of ovarian cancer stem cells

2016 ◽  
Vol 48 (8) ◽  
pp. e255-e255 ◽  
Author(s):  
Dae Kyoung Kim ◽  
Eun Jin Seo ◽  
Eun J Choi ◽  
Su In Lee ◽  
Yang Woo Kwon ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Crucial Role ◽  
The Self ◽  
Ovarian Cancer Stem Cells ◽  
Self Renewal

scholarly journals Emerging Role of E2F Family in Cancer Stem Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Dan Xie ◽  
Qin Pei ◽  
Jingyuan Li ◽  
Xue Wan ◽  
Ting Ye
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Tumor Development ◽  
Transcriptional Repressors ◽  
Cellular Processes ◽  
Damage Response ◽  
Prevent Tumor Growth ◽  
Cycle Regulation

The E2F family of transcription factors (E2Fs) consist of eight genes in mammals. These genes encode ten proteins that are usually classified as transcriptional activators or transcriptional repressors. E2Fs are important for many cellular processes, from their canonical role in cell cycle regulation to other roles in angiogenesis, the DNA damage response and apoptosis. A growing body of evidence demonstrates that cancer stem cells (CSCs) are key players in tumor development, metastasis, drug resistance and recurrence. This review focuses on the role of E2Fs in CSCs and notes that many signals can regulate the activities of E2Fs, which in turn can transcriptionally regulate many different targets to contribute to various biological characteristics of CSCs, such as proliferation, self-renewal, metastasis, and drug resistance. Therefore, E2Fs may be promising biomarkers and therapeutic targets associated with CSCs pathologies. Finally, exploring therapeutic strategies for E2Fs may result in disruption of CSCs, which may prevent tumor growth, metastasis, and drug resistance.

scholarly journals The Role of Smoothened in Cancer

2020 ◽  
Vol 21 (18) ◽  
pp. 6863 ◽  
Author(s):  
Kuo-Shyang Jeng ◽  
I-Shyan Sheen ◽  
Chuen-Miin Leu ◽  
Ping-Hui Tseng ◽  
Chiung-Fang Chang
Keyword(s):  
Stem Cells ◽  
Signaling Pathway ◽  
Cell Activity ◽  
Therapeutic Approaches ◽  
Colon Cancers ◽  
Stem Cell Activity ◽  
Different Types ◽  
Hh Signaling ◽  
Novel Therapeutic

Smoothened (SMO) belongs to the Hedgehog (HH) signaling pathway, which regulates cell growth, migration, invasion and stem cells in cancer. The HH signaling pathway includes both canonical and noncanonical pathways. The canonical HH pathway functions through major HH molecules such as HH ligands, PTCH, SMO and GLI, whereas the noncanonical HH pathway involves the activation of SMO or GLI through other pathways. The role of SMO has been discussed in different types of cancer, including breast, liver, pancreatic and colon cancers. SMO expression correlates with tumor size, invasiveness, metastasis and recurrence. In addition, SMO inhibitors can suppress cancer formation, reduce the proliferation of cancer cells, trigger apoptosis and suppress cancer stem cell activity. A better understanding of the role of SMO in cancer could contribute to the development of novel therapeutic approaches.

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