Figure - uploaded by Moath Alqaraleh
Content may be subject to copyright.
Contribution of CD44v in different type of cancer

Contribution of CD44v in different type of cancer

Source publication
Article
Full-text available
Breast cancer (BC) is among the most prevalent type of malignancy affecting females worldwide. BC is classified into different types according to the status of the expression of receptors such as estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and progesterone receptor (PR). Androgen receptor (AR) appears to be a promising...

Contexts in source publication

Context 1
... chain reaction or IHC) or using different primary anti-CD44 antibodies that may not recognize the CD44v epitopes [29]. For more detailed information regarding some cancer type's relation with CD44v, see Table 2. ...
Context 2
... chain reaction or IHC) or using different primary anti-CD44 antibodies that may not recognize the CD44v epitopes [29]. For more detailed information regarding some cancer type's relation with CD44v, see Table 2. ...

Similar publications

Article
Full-text available
In this work, we compared mRNA levels of Hyaluronan (HA) metabolism members and BRCA genes, known to be involved in the tumoral process, between tumor and non-tumor adjacent tissue and its correlation with previously proposed biomarkers (ER, PR, HER2 and KI67) in order to assess their value as a progression biomarkers. We show alteration in HA meta...

Citations

... CD44 alongside receptor tyrosine kinase (RKT) articulates breast CSCs differentiation and migration. Its impeding results in hindering properties of breast CSCs such as cell adhesion, malignancy, progression, metastasis, EMT, and drug resistance (Al-Othman et al., 2020). Hence CD44 is regarded as a predictive marker in breast CSCs mediated resistance. ...
Article
Full-text available
Breast cancer (BC) is the most prevalent neoplasm among women. Genetic and environmental factors lead to BC development and on this basis, several preventive – screening and therapeutic interventions have been developed. Hormones, both in the form of endogenous hormonal signaling or hormonal contraceptives, play an important role in BC pathogenesis and progression. On top of these, breast microbiota includes both species with an immunomodulatory activity enhancing the host’s response against cancer cells and species producing proinflammatory cytokines associated with BC development. Identification of novel multitargeted therapeutic agents with poly-pharmacological potential is a dire need to combat advanced and metastatic BC. A growing body of research has emphasized the potential of natural compounds derived from medicinal plants and microbial species as complementary BC treatment regimens, including dietary supplements and probiotics. In particular, extracts from plants such as Artemisia monosperma Delile, Origanum dayi Post, Urtica membranacea Poir. ex Savigny, Krameria lappacea (Dombey) Burdet & B.B. Simpson and metabolites extracted from microbes such as Deinococcus radiodurans and Streptomycetes strains as well as probiotics like Bacillus coagulans and Lactobacillus brevis MK05 have exhibited antitumor effects in the form of antiproliferative and cytotoxic activity, increase in tumors’ chemosensitivity, antioxidant activity and modulation of BC – associated molecular pathways. Further, bioactive compounds like 3,3’-diindolylmethane, epigallocatechin gallate, genistein, rutin, resveratrol, lycopene, sulforaphane, silibinin, rosmarinic acid, and shikonin are of special interest for the researchers and clinicians because these natural agents have multimodal action and act via multiple ways in managing the BC and most of these agents are regularly available in our food and fruit diets. Evidence from clinical trials suggests that such products had major potential in enhancing the effectiveness of conventional antitumor agents and decreasing their side effects. We here provide a comprehensive review of the therapeutic effects and mechanistic underpinnings of medicinal plants and microbial metabolites in BC management. The future perspectives on the translation of these findings to the personalized treatment of BC are provided and discussed.
... CD44 is a membrane receptor that interacts with several molecules and displays hyaluronic acid as its main ligand [131]. In the breast, CD44 is a marker of cancer stem cells and is related to propagation, metastasis and resistance to chemotherapy [132]. To target CD44, Alshaer et al. constructed aptamer-guided liposomes containing siRNA against the luciferase gene [133]. ...
Article
Ligand-mediated targeting represents the cutting edge in precision-guided therapy for several diseases. Surface engineering of nanomedicines with ligands exhibiting selective or tailored affinity for overexpressed biomolecules of a specific disease may increase therapeutic efficiency and reduce side effects and recurrence. This review focuses on newly developed approaches and strategies to improve treatment and overcome the mechanisms associated with breast cancer resistance.
... In TNBC, several targets have been exploited such as the CD44 receptor, a cell adhesion membrane glycoprotein overexpressed on many cancer types including triple-negative breast cancer [176], or EGFR-1 receptors. Hyaluronic acid is a CD44 receptor ligand, and, for this reason, it is grafted on the surface of polymeric nanosystems to obtain their selective localization in these cancer cells. ...
Article
Full-text available
Breast cancer is one of the most frequently diagnosed tumors and the second leading cause of cancer death in women worldwide. The use of nanosystems specifically targeted to tumor cells (active targeting) can be an excellent therapeutic tool to improve and optimize current chemotherapy for this type of neoplasm, since they make it possible to reduce the toxicity and, in some cases, increase the efficacy of antineoplastic drugs. Currently, there are 14 nanomedicines that have reached the clinic for the treatment of breast cancer, 4 of which are already approved (Kadcyla®, Enhertu®, Trodelvy®, and Abraxane®). Most of these nanomedicines are antibody–drug conjugates. In the case of HER-2-positive breast cancer, these conjugates (Kadcyla®, Enhertu®, Trastuzumab-duocarmycin, RC48, and HT19-MMAF) target HER-2 receptors, and incorporate maytansinoid, deruxtecan, duocarmicyn, or auristatins as antineoplastics. In TNBC these conjugates (Trodelvy®, Glembatumumab-Vedotin, Ladiratuzumab-vedotin, Cofetuzumab-pelidotin, and PF-06647263) are directed against various targets, in particular Trop-2 glycoprotein, NMB glycoprotein, Zinc transporter LIV-1, and Ephrin receptor-4, to achieve this selective accumulation, and include campthotecins, calicheamins, or auristatins as drugs. Apart from the antibody–drug conjugates, there are other active targeted nanosystems that have reached the clinic for the treatment of these tumors such as Abraxane® and Nab-rapamicyn (albumin nanoparticles entrapping placlitaxel and rapamycin respectively) and various liposomes (MM-302, C225-ILS-Dox, and MM-310) loaded with doxorubicin or docetaxel and coated with ligands targeted to Ephrin A2, EPGF, or HER-2 receptors. In this work, all these active targeted nanomedicines are discussed, analyzing their advantages and disadvantages over conventional chemotherapy as well as the challenges involved in their lab to clinical translation. In addition, examples of formulations developed and evaluated at the preclinical level are also discussed.
... The important domain in the formation of isoforms is the extracellular domain. Diffe rent variants arise due to alternative splicing occurring in the exons of this domain [6,7]. ...
... CD44v is associated inflammation and various types of cancer. Also up-regulation of CD44v promotes tumor progression and metastasis [6]. ...
... The decrease in CD44 suggested that it decreased the motility of the cells in both cell lines. As a matter of fact, it has been reported that there are different variants of CD44 and that CD44v5, CD44v6, CD44v8-10 from these variants show different expression in breast cancer [6]. In addition, Afifiy et al. indicated that CD44s and CD44v6 play a role in breast cancer cell adhesion, motility and invasion through their interaction with Hyaluronic acid (HA). ...
Article
Full-text available
Background. Hyaluronan receptors play a role in various types of cancer. However, the changes oc- curring in CD44 and RHAMM after rapamycin administration are waiting to be explained. We aimed to investigate the changes in the hyaluronic acid receptors CD44 and RHAMM after rapamycin was administered in MCF-7 and MDA-MB-231 cell lines. Materials and methods. MCF-7 and MDA-MB-231 cell lines were cultured un- der standard conditions. The cell lines were stained with primary antibodies of CD44 and RHAMM to show the proteins. The H-score values were determined by the intensity of immunoreactivity. QRT-PCR was used to detect the expression of CD44 and RHAMM. Results. In the MCF-7 and MDA-MB-231 cell lines, the immunoreactivity of CD44 and RHAMM decreased at the 24th hour after rapamycin administration compared to the control group. According to the qRT-PCR results, the expression of CD44 (p < 0.033), and RHAMM (p < 0.0002) decreased in the rapamycin group compared to the control group. Conclusions. Rapamycin reduced the effect of hyalorunan receptors on breast cancer cell lines. Thus, the importance of the extracellular matrix in breast cancer has emerged once again.
... [12][13][14][15] CD44 facilitates the development of cancer through activating central key signaling pathways, including the renin-angiotensin system (RAS)/MAPK/ERK, Rho Rho guanosine triphosphate hydrolases (GTPases), and PI3K/ protein kinase B (AKT) pathways. 16,17 As one distinctive MAPK cascade, the MAPK/ERK cascade is primarily described as a transducer of extracellular signals and it participates in the regulation of several fundamental processes such as proliferation, migration, metabolism, differentiation, and angiogenesis. [18][19][20] Here, we focus on the expression, clinical significance, biological roles, and underlying molecular mechanisms of PDRG1 in GBM. ...
Article
Full-text available
P53 and DNA damage-regulated gene1 (PDRG1) is overexpressed in diverse carcinomas. Here, we discover that PDRG1 is overexpressed in glioblastoma multiforme (GBM). However, the clinical significance, biological role and underlying molecular mechanisms of PDRG1 in GBM remain unclear. PDRG1 was aberrantly overexpressed in glioma, especially prevalent in GBM and correlated with poor clinicopathologic features of glioma. The risk score, operational feature curve analysis, Kaplan-Meier curve, univariate and multivariate cox regression analysis indicated that PDRG1 was an independent prognostic indicator and significantly correlates with disease progression of glioma. A prognostic nomogram was constructed to predict the survival risk of individual patient. The function and pathway enrichment analysis of PDRG1 in TCGA cohort was performed. PDRG1 knockdown significantly inhibited the migration and proliferation of GBM cells in vitro and in vivo. Transcriptome sequencing analysis of PDRG1 knockdown U118 cells indicated that biological regulation adhesion, growth and death, cell motility, cell adhesion molecular and proteoglycans in cancer were significantly enriched. Importantly, we found that the expression of adhesion molecule CD44 was regulated by PDRG1 in GBM. We found that PDRG1 promoted the migration and proliferation of GBM cells via MEK/ERK/CD44 pathway. Our findings provide proof that PDRG1 upregulation predicts progression and poor prognosis in human gliomas especially in IDH wt glioma patients. The study provides new evidence that PDRG1 regulates the expression of CD44 in GBM cells and might promote the migration and proliferation viaMEK/ERK/CD44pathway. PDRG1 might be a novel diagnostic indicator and promising therapeutic target for GBM.
... The CD44 is an essential molecular marker of cancer stem cells in breast cancer. The CD44 is expressed on the surface of highly metastatic breast cancer cells as a co-receptor for a broad diversity of extracellular matrix ligands, primarily HA [41]. Recently, a paper demonstrated that the interaction of HA with CD44 activates AMPK and autophagic pathways [42]. ...
Article
Full-text available
The microenvironment for tumor growth and developing metastasis should be essential. This study demonstrated that the hyaluronic acid synthase 3 (HAS3) protein and its enzymatic product hyaluronic acid (HA) encompassed in the subcutaneous extracellular matrix can attenuate the invasion of human breast tumor cells. Decreased HA levels in subcutaneous Has3-KO mouse tissues promoted orthotopic breast cancer (E0771) cell-derived allograft tumor growth. MDA-MB-231 cells premixed with higher concentration HA attenuate tumor growth in xenografted nude mice. Human patient-derived xenotransplantation (PDX) experiments found that HA selected the highly migratory breast cancer cells with CD44 expression accumulated in the tumor/stroma junction. In conclusion, HAS3 and HA were detected in the stroma breast tissues at a high level attenuates effects for induced breast cancer cell death, and inhibit the cancer cells invasion at the initial stage. However, the highly migratory cancer cells were resistant to the HA-mediated effects with unknown mechanisms.
... The signaling properties of CD44 result not only from its association with HA polymers but also its interactions with other cell surface and extracellular proteins (e.g., growth factor receptors, osteopontin, metalloproteinases, and collagens) [71]. The small, intracellular domain (ICD) of CD44 additionally binds to intracellular adaptor and cytoskeletal proteins [72]. The binding of HA polymers to CD44 promotes homotypic CD44 clustering that can activate or impede oncogenic signaling cascades depending upon the HA polymer size and its partnering with other proteins. ...
Article
Full-text available
Signaling from an actively remodeling extracellular matrix (ECM) has emerged as a critical factor in regulating both the repair of tissue injuries and the progression of diseases such as metastatic cancer. Hyaluronan (HA) is a major component of the ECM that normally functions in tissue injury to sequentially promote then suppress inflammation and fibrosis, a duality in which is featured, and regulated in, wound repair. These essential response-to-injury functions of HA in the microenvironment are hijacked by tumor cells for invasion and avoidance of immune detection. In this review, we first discuss the numerous size-dependent functions of HA and emphasize the multifunctional nature of two of its receptors (CD44 and RHAMM) in regulating the signaling duality of HA in excisional wound healing. This is followed by a discussion of how HA metabolism is de-regulated in malignant progression and how targeting HA might be used to better manage breast cancer progression.
... Studies in SCID mice which were transplanted with a small number (around 100 cells) of these BCSCs (CD44 + /CD24 -/Lin -) showed the development of tumors with a similar molecular heterogeneity as the original tumor, validating that CSCs as drivers of cancer recurrence, metastasis and treatment resistance [51]. Clinical data has shown that cells with CD44 + CD24 -/Low and ALDH1 + expression are more tumorigenic and result in poor survival rates in patients [52]. July 26, 2021 Volume 13 Issue 7 CD44, a transmembrane glycoprotein that acts as a receptor for various growth factors and ligands present in the extracellular matrix [53], is responsible for maintenance of BCSC population by activating Ras-MAPK and PI3K/AKT pathways [54] and imparts treatment resistance through the activation of p62-associated nuclear factor erythroid2-related factor 2[55]. ...
Article
Full-text available
As per the latest Globocan statistics, the high prevalence rate of breast cancer in low- and middle-income countries has led to it becoming the most common cancer to be diagnosed, hence posing a major public health challenge. As per this data, more than 11.7% of the estimated new cancer cases in 2020 were due to breast cancer. A small but significant subpopulation of cells with self- renewing ability are present in the tumor stroma and have been given the nomenclature of cancer stem cells (CSCs). These cells display a high degree of plasticity owing to their ability to transition from the slowly cycling quiescent phase to the actively proliferating phenotype. This attribute of CSCs allows them to differentiate into various cell types having diverse functions. Breast CSCs have a pivotal role in development, metastasis, treatment resistance and relapse of breast cancers. This review focuses on the pathways regulating breast CSC maintenance and the current strategies that are being explored for directing the development of novel, targeted, therapeutic approaches for limiting and eradicating this aberrant stem cell population.
... Studies in SCID mice which were transplanted with a small number (around 100 cells) of these BCSCs (CD44 + /CD24 -/Lin -) showed the development of tumors with a similar molecular heterogeneity as the original tumor, validating that CSCs as drivers of cancer recurrence, metastasis and treatment resistance [51]. Clinical data has shown that cells with CD44 + CD24 -/Low and ALDH1 + expression are more tumorigenic and result in poor survival rates in patients [52]. July 26, 2021 Volume 13 Issue 7 CD44, a transmembrane glycoprotein that acts as a receptor for various growth factors and ligands present in the extracellular matrix [53], is responsible for maintenance of BCSC population by activating Ras-MAPK and PI3K/AKT pathways [54] and imparts treatment resistance through the activation of p62-associated nuclear factor erythroid2-related factor 2[55]. ...
Article
As per the latest Globocan statistics, the high prevalence rate of breast cancer in low- and middle-income countries has led to it becoming the most common cancer to be diagnosed, hence posing a major public health challenge. As per this data, more than 11.7% of the estimated new cancer cases in 2020 were due to breast cancer. A small but significant subpopulation of cells with self- renewing ability are present in the tumor stroma and have been given the nomenclature of cancer stem cells (CSCs). These cells display a high degree of plasticity owing to their ability to transition from the slowly cycling quiescent phase to the actively proliferating phenotype. This attribute of CSCs allows them to differentiate into various cell types having diverse functions. Breast CSCs have a pivotal role in development, metastasis, treatment resistance and relapse of breast cancers. This review focuses on the pathways regulating breast CSC maintenance and the current strategies that are being explored for directing the development of novel, targeted, therapeutic approaches for limiting and eradicating this aberrant stem cell population.
... Colacino et al., demonstrated that ALDH + and CD44 + /CD24 − breast cancer cells possesses higher mammosphere forming potential, and express higher levels of stemness and EMTrelated genes [35]. Incidentally, recent studies also suggested the presence of heterogenous populations among the sorted breast CSCs based on the presence and absence of ALDH [36,37]. Our study corroborated well with that of Colacino et al., depicting the sorted breast CSCs were 98% ALDH + , exhibited increased in vitro tumorigenicity with the higher expression of mesenchymal and stemness markers. ...
Article
Breast cancer stem cells (CSCs) are distinct CD44⁺-subpopulations that are involved in metastasis and chemoresistance. However, the underlying molecular mechanism of CD44 in breast CSCs-mediated tumorigenesis remains elusive. We observed high CD44 expression in advanced-stage clinical breast tumor samples. CD44 activation in breast CSCs sorted from various triple negative breast cancer (TNBC) cell lines induced proliferation, migration, invasion, mammosphere formation that were reversed in presence of inhibitor, 4-methyl umbelliferone or CD44 silencing. CD44 activation in breast CSCs induced Src, Akt, and nuclear translocation of pSTAT3. PCR arrays revealed differential expression of a metabolic gene, Lipoprotein lipase (LPL), and transcription factor, SNAI3. Differential transcriptional regulation of LPL by pSTAT3 and SNAI3 was confirmed by promoter-reporter and chromatin immunoprecipitation analysis. Orthotopic xenograft murine breast tumor model revealed high tumorigenicity of CD24⁻/CD44⁺-breast CSCs as compared with CD24⁺-breast cancer cells. Furthermore, stable breast CSCs-CD44 shRNA and/or intratumoral administration of Tetrahydrolipstatin (LPL inhibitor) abrogated tumor progression and neoangiogenesis. Thus, LPL serves as a potential target for an efficacious therapeutics against aggressive breast cancer.