CD44: A Multifunctional Mediator of Cancer Progression

Mesrati, Malak Hassn; Syafruddin, Saiful Effendi; Mohtar, M. Aiman; Syahir, Amir

doi:10.3390/biom11121850

Cited by 252 publications

(217 citation statements)

References 227 publications

(209 reference statements)

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“…On the other hand, cancer cells are normally characterized as an overexpression of various molecular receptors [ 48 , 49 ]. For example, folate receptors are overexpressed in malignant cells such as Y79 human retinoblastoma cells compared with normal cells such as ARPE-19 cells [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Reactive Oxygen Species and Folate Receptor-Targeted Nanophotosensitizers Composed of Folic Acid-Conjugated and Poly(ethylene glycol)-Chlorin e6 Tetramer Having Diselenide Linkages for Targeted Photodynamic Treatment of Cancer Cells

Yang

Jeong

Kook

et al. 2022

IJMS

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Folic acid-conjugated nanophotosensitizers composed of folic acid (FA), poly(ethylene glycol) (PEG) and chlorin e6 (Ce6) tetramer were synthesized using diselenide linkages for reactive oxygen species (ROS)- and folate receptor-specific delivery of photosensitizers. Ce6 was conjugated with 3-[3-(2-carboxyethoxy)-2,2-bis(2-carboxyethoxymethyl)propoxy]propanoic acid (tetra acid, or TA) to make Ce6 tetramer via selenocystamine linkages (TA-sese-Ce6 conjugates). In the carboxylic acid end group of the TA-sese-Ce6 conjugates, FA-PEG was attached again using selenocystamine linkages to make FA-PEG/TA-sese-Ce6 conjugates (abbreviated as FAPEGtaCe6 conjugates). Nanophotosensitizers were fabricated by a dialysis procedure. In the morphological observations, they showed spherical shapes with small diameters of less than 200 nm. Stability of the aqueous FAPEGtaCe6 nanophotosensitizer solution was maintained (i.e., their particle sizes were not significantly changed until 7 days later). When H2O2 was added to the nanophotosensitizer solution, the particle size distribution was changed from a monomodal pattern to a multimodal pattern. In addition, the fluorescence intensity and Ce6 release rate from the nanophotosensitizers were also increased by the addition of H2O2. These results indicated that the nanophotosensitizers had ROS-sensitive properties. In an in vitro cell culture study, an FAPEGtaCe6 nanophotosensitizer treatment against cancer cells increased the Ce6 uptake ratio, ROS generation and light-irradiated cytotoxicity (phototoxicity) compared with Ce6 alone against various cancer cells. When the folic acid was pretreated to block the folate receptors of the Y79 cells and KB cells (folate receptor-overexpressing cells), the intracellular Ce6 uptake, ROS generation and thereby phototoxicity were decreased, while the MCF-7 cells did not significantly respond to blocking of the folate receptors. These results indicated that they could be delivered by a folate receptor-mediated pathway. Furthermore, an in vivo pulmonary metastasis model using Y79 cells showed folate receptor-specific delivery of FAPEGtaCe6 nanophotosensitizers. When folic acid was pre-administered, the fluorescence intensity of the lungs was significantly decreased, indicating that the FAPEGtaCe6 nanophotosensitizers had folate receptor specificity in vitro and in vivo. We suggest that FAPEGtaCe6 nanophotosensitizers are promising candidates for a targeted photodynamic therapy (PDT) approach against cancer cells.

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Section: Discussionmentioning

confidence: 99%

Reactive Oxygen Species and Folate Receptor-Targeted Nanophotosensitizers Composed of Folic Acid-Conjugated and Poly(ethylene glycol)-Chlorin e6 Tetramer Having Diselenide Linkages for Targeted Photodynamic Treatment of Cancer Cells

Yang

Jeong

Kook

et al. 2022

IJMS

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“…ECM components, including glycoproteins, glycosaminoglycans (GAG), proteoglycans, soluble molecules, and fibrillar proteins, can directly interact with specific receptors on the tumor cell surface, regulating several aspects of their biology. In this context, particularly relevant is the CD44/hyaluronic acid (HA) axis [ 11 ], which is targeted in different therapeutic approaches, or the CXCR4/SDF1 axis driving bone marrow (BM) homing of tumor cells. ECM components can also contribute to the onset of an immunosuppressive milieu since many molecules such as the serine protease plasmin, matrix metalloprotease (MMP)-2 and MMP9, or thrombospondin-1 disrupt the latent form of tumor growth factor (TGF)-β (LAP–TGF-β) with the release of an active form of the cytokine [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Tumor Microenvironment and Hydrogel-Based 3D Cancer Models for In Vitro Testing Immunotherapies

Vitale

Marzagalli²,

Scaglione

et al. 2022

Cancers

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In recent years, immunotherapy has emerged as a promising novel therapeutic strategy for cancer treatment. In a relevant percentage of patients, however, clinical benefits are lower than expected, pushing researchers to deeply analyze the immune responses against tumors and find more reliable and efficient tools to predict the individual response to therapy. Novel tissue engineering strategies can be adopted to realize in vitro fully humanized matrix-based models, as a compromise between standard two-dimensional (2D) cell cultures and animal tests, which are costly and hardly usable in personalized medicine. In this review, we describe the main mechanisms allowing cancer cells to escape the immune surveillance, which may play a significant role in the failure of immunotherapies. In particular, we discuss the role of the tumor microenvironment (TME) in the establishment of a milieu that greatly favors cancer malignant progression and impact on the interactions with immune cells. Then, we present an overview of the recent in vitro engineered preclinical three-dimensional (3D) models that have been adopted to resemble the interplays between cancer and immune cells and for testing current therapies and immunotherapeutic approaches. Specifically, we focus on 3D hydrogel-based tools based on different types of polymers, discussing the suitability of each of them in reproducing the TME key features based on their intrinsic or tunable characteristics. Finally, we introduce the possibility to combine the 3D models with technological fluid dynamics platforms, reproducing the dynamic complex interactions between tumor cells and immune effectors migrated in situ via the systemic circulation, pointing out the challenges that still have to be overcome for setting more predictive preclinical assays.

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“…Based on their structures, CAMs can be classified into four major groups: integrins, cadherins, selectins, and the immunoglobulin superfamily CAM (IgCAM) ( 12 , 13 ). CD44 is an essential cell surface glycoprotein involved in cell-to-cell adhesion ( 14 ). Therefore, we considered CD44 as a CAM in this context.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Cell Adhesion Molecules in Endocrine-Related Cancers: A Concise Outlook

et al. 2022

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Chemotherapy is a critical treatment for endocrine-related cancers; however, chemoresistance and disease recurrence remain a challenge. The interplay between cancer cells and the tumor microenvironment via cell adhesion molecules (CAMs) promotes drug resistance, known as cell adhesion-mediated drug resistance (CAM-DR). CAMs are cell surface molecules that facilitate cell-to-cell or cell-to-extracellular matrix binding. CAMs exert an adhesion effect and trigger intracellular signaling that regulates cancer cell stemness maintenance, survival, proliferation, metastasis, epithelial–mesenchymal transition, and drug resistance. To understand these mechanisms, this review focuses on the role of CD44, cadherins, selectins, and integrins in CAM-DR in endocrine-related cancers.

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CD44: A Multifunctional Mediator of Cancer Progression

Cited by 252 publications

References 227 publications

Reactive Oxygen Species and Folate Receptor-Targeted Nanophotosensitizers Composed of Folic Acid-Conjugated and Poly(ethylene glycol)-Chlorin e6 Tetramer Having Diselenide Linkages for Targeted Photodynamic Treatment of Cancer Cells

Reactive Oxygen Species and Folate Receptor-Targeted Nanophotosensitizers Composed of Folic Acid-Conjugated and Poly(ethylene glycol)-Chlorin e6 Tetramer Having Diselenide Linkages for Targeted Photodynamic Treatment of Cancer Cells

Tumor Microenvironment and Hydrogel-Based 3D Cancer Models for In Vitro Testing Immunotherapies

Mechanisms of Cell Adhesion Molecules in Endocrine-Related Cancers: A Concise Outlook

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