CD44 in Bone Metastasis Development: A Key Player in the Fate Decisions of the Invading Cells?

Zer, Noy Shir; Ben-Ghedalia-Peled, Noa; Gheber, Levi A.; Vago, Razi

doi:10.1007/s10585-023-10203-z

Cited by 7 publications

(4 citation statements)

References 100 publications

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“…17,35 The high flux of calcium may further lead to enhanced activation of various signaling, transducing cascades such as CD44, Wnt, mTOR, cadherins, etc. 36,38,39 This possible calcium effect is of a particular importance within the endosteal niche, where calcium, Wnt ligands, BMPs, and other trapped growth factors can be released following the onset of the "vicious cycle," degradation of the ECM and also can be secreted by the natural hub niche cells that are harnessed by the invading cells. 36,39 Cells in tissues and organs reside within a three-dimensional microenvironment composed of ECM and surrounding cells that play a crucial role in normal development and homeostasis.…”

Section: Discussionmentioning

confidence: 99%

“…36,38,39 This possible calcium effect is of a particular importance within the endosteal niche, where calcium, Wnt ligands, BMPs, and other trapped growth factors can be released following the onset of the "vicious cycle," degradation of the ECM and also can be secreted by the natural hub niche cells that are harnessed by the invading cells. 36,39 Cells in tissues and organs reside within a three-dimensional microenvironment composed of ECM and surrounding cells that play a crucial role in normal development and homeostasis. However, the physical and organic landscapes also play a pivotal role in shaping cellular activities, notably with respect to tumor progression.…”

Section: Discussionmentioning

confidence: 99%

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Bone Endosteal Mimics Regulates Breast Cancer Development and Phenotype

Ben Ghedalia Peled,

Hoffman,

Barsky

et al. 2024

Biomacromolecules

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Bone is a frequent site for metastatic development in various cancer types, including breast cancer, with a grim prognosis due to the distinct bone environment. Despite considerable advances, our understanding of the underlying processes leading to bone metastasis progression remains elusive. Here, we applied a bioactive three-dimensional (3D) model capable of mimicking the endosteal bone microenvironment. MDA-MB-231 and MCF7 breast cancer cells were cultured on the scaffolds, and their behaviors and the effects of the biomaterial on the cells were examined over time. We demonstrated that close interactions between the cells and the biomaterial affect their proliferation rates and the expression of c-Myc, cyclin D, and KI67, leading to cell cycle arrest. Moreover, invasion assays revealed increased invasiveness within this microenvironment. Our findings suggest a dual role for endosteal mimicking signals, influencing cell fate and potentially acting as a double-edged sword, shuttling between cell cycle arrest and more active, aggressive states.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bone Endosteal Mimics Regulates Breast Cancer Development and Phenotype

Ben Ghedalia Peled,

Hoffman,

Barsky

et al. 2024

Biomacromolecules

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“…HA’s potential also was revealed for cancer treatment thanks to its interaction with the CD44 R. This receptor plays a crucial role in the invasion and metastatic processes of several human cancers [ 143 ]. Additionally, it is involved in mesenchymal epithelial transition [ 144 , 145 ], drug resistance [ 146 ], and resistance to chemo- and radiotherapy [ 147 ], and it is also a marker for cancer stem cells as well as gastric and breast cancers [ 148 , 149 , 150 ]. For this, Zhang et al developed a cleavable PEGylated HA nano-drug delivery system in order to improve the active tumor targeting, tumor cell uptake efficiency, and circulation time of doxorubicin in vitro and in vivo [ 16 ].…”

Section: Ha As a Powerful Bioactive Moleculementioning

confidence: 99%

Hyaluronic Acid: A Powerful Biomolecule with Wide-Ranging Applications—A Comprehensive Review

Iaconisi,

Lunetti,

Gallo

et al. 2023

IJMS

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Hyaluronic acid (HA) is a glycosaminoglycan widely distributed in the human body, especially in body fluids and the extracellular matrix of tissues. It plays a crucial role not only in maintaining tissue hydration but also in cellular processes such as proliferation, differentiation, and the inflammatory response. HA has demonstrated its efficacy as a powerful bioactive molecule not only for skin antiaging but also in atherosclerosis, cancer, and other pathological conditions. Due to its biocompatibility, biodegradability, non-toxicity, and non-immunogenicity, several HA-based biomedical products have been developed. There is an increasing focus on optimizing HA production processes to achieve high-quality, efficient, and cost-effective products. This review discusses HA’s structure, properties, and production through microbial fermentation. Furthermore, it highlights the bioactive applications of HA in emerging sectors of biomedicine.

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“…This review focuses on the duality in cancer of two multifunctional proteins, CD44 and RHAMM/HMMR because both are particularly implicated in metastatic progression. [ 21,22,24–26 ] Importantly they are partner proteins in sensing remodeling, wound‐like microenvironments that tumors initiate in and metastasize into. [ 27–30 ] This focus can be expanded to other oncogenic proteins since it illustrates an emerging perspective that a paradigm shift away from classifying proteins exclusively as suppressors or promoters is required to develop more effective therapies for managing metastatic cancer.…”

Section: Introductionmentioning

confidence: 99%

CD44 and RHAMM Are Microenvironmental Sensors with Dual Metastasis Promoter and Suppressor Functions

Tolg,

Hill,

Turley

2024

Advanced Biology

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The progression of primary tumors to metastases remains a significant roadblock to the treatment of most cancers. Emerging evidence has identified genes that specifically affect metastasis and are potential therapeutic targets for managing tumor progression. However, these genes can have dual tumor promoter and suppressor functions that are contextual in manifestation, and that complicate their development as targeted therapies. CD44 and RHAMM/HMMR are examples of multifunctional proteins that can either promote or suppress metastases, as demonstrated in experimental models. These two proteins can be viewed as microenvironmental sensors and this minireview addresses the known mechanistic underpinnings that may determine their metastasis suppressor versus promoter functions. Leveraging this mechanistic knowledge for CD44, RHAMM, and other multifunctional proteins is predicted to improve the precision of therapeutic targeting to achieve more effective management of metastasis.

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CD44 in Bone Metastasis Development: A Key Player in the Fate Decisions of the Invading Cells?

Cited by 7 publications

References 100 publications

Bone Endosteal Mimics Regulates Breast Cancer Development and Phenotype

Bone Endosteal Mimics Regulates Breast Cancer Development and Phenotype

Hyaluronic Acid: A Powerful Biomolecule with Wide-Ranging Applications—A Comprehensive Review

CD44 and RHAMM Are Microenvironmental Sensors with Dual Metastasis Promoter and Suppressor Functions

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