Involvement of CD44, a molecule with a thousand faces, in cancer dissemination

Naor, David; Wallach-Dayan, Shulamit B.; Zahalka, Muayad A.; Sionov, Ronit Vogt

doi:10.1016/j.semcancer.2008.03.015

Cited by 261 publications

(165 citation statements)

References 56 publications

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“…In addition, Mikami et al reported that CD44v3 and v6 were overexpressed in extrahepatic bile duct carcinomas and were linked with carcinoma cell differentiation [19]. Interestingly, mouse malignant lymphoma cell lines transfected with CD44v4-10, but not CD44s, displayed enhanced invasion of the peripheral lymph nodes [20]. This evidence lends support to the potential role of CD44s and some of its variants in promoting the metastatic phenotype of cancer cells.…”

Section: Introductionmentioning

confidence: 81%

Silencing of CD44 by siRNA suppressed invasion, migration and adhesion to matrix, but not secretion of MMPs, of cholangiocarcinoma cells

Pongcharoen

Jinawath

Tohtong

2011

Clin Exp Metastasis

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We studied the expression pattern and the role of CD44 in regulating the malignant behavior of two cholangiocarcinoma (CCA) cell lines which expressed different levels of CD44 using the siRNA technique. KKU-100, the high CD44 expresser, exhibited a high degree of in vitro invasiveness, migration and adhesion to Matrigel compared to HuCCA-1. Silencing of CD44 by siRNA did not have a significant effect on cell proliferation. However, in vitro invasiveness, directional migration (chemotaxis) and adhesion to Matrigel were markedly reduced in both cell lines, although chemokinesis and MMP secretion were variable, demonstrating the distinct functional role and requirement for CD44 in different cellular activities and in different cell types. In addition, immunohistochemical analysis suggested that CD44 may be involved in the differentiation process or tumor progression, depending on the macroscopic type of CCA. Taken together, our data indicate that CD44 is an important requirement for the invasive phenotype of CCA cells, although the role that CD44 plays may vary depending on the CCA type and the cellular activity in which it is engaged.

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Section: Introductionmentioning

confidence: 81%

Silencing of CD44 by siRNA suppressed invasion, migration and adhesion to matrix, but not secretion of MMPs, of cholangiocarcinoma cells

Pongcharoen

Jinawath

Tohtong

2011

Clin Exp Metastasis

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“…76,77 CD44 is a transmembrane glycoprotein that serves as a receptor for various components of extracellular matrix. 78,79 Its most important roles include intermediation in cell-cell and cellmatrix interactions, as well as cancer cell migration. Thus, CD44 binding regulates CSCs survival, self-renewal, and chemoresistance.…”

Section: 74mentioning

confidence: 99%

Quinoline based mono- and bis-(thio)carbohydrazones: synthesis, anticancer activity in 2D and 3D cancer and cancer stem cell models

Božić

Marinković

Bjelogrlić³

et al. 2016

RSC Adv.

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A comparative study of antitumor activity of mono-and bis-quinoline based (thio)carbohydrazones was investigated by a series of tests on two human malignant cell lines: acute monocytic leukemia (THP-1) and pancreatic adenocarcinoma cancer stem cells (AsPC-1). Thiocarbohydrazones (TCHs) revealed superior pro-apoptotic activity over carbohydrazones (CHs) on both tested cell phenotypes, also displaying multi-target profile activities. Programmed cell death triggered by TCHs was partially caspasedependent, mainly caspase-8 related. Activity against cancer stem cells (CSCs) was evaluated on 2D monolayers and 3D spheroidal models, where two out of three tested bis-TCHs successfully stimulated apoptosis accompanied by a reduction in size of treated spheres. Additionally, all bis-TCHs induced significant decrease in percentage of CD44-expressing AsPC-1 cells that indicate on their ability to induce reprogramming of CSC phenotype. Current results highly support further assessment of bisTCHs in order to specify their specific targets in cancer cells and particularly in the CSCs subpopulation.

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“…CD44 exists in various isoforms, the standard form (CD44s) and the variant forms (CD44v1-10), all of which can bind hyaluronan (11)(12)(13)(14). Increased hyaluronan synthesis and increased expression of CD44 have been observed in aggressive breast cancer cells (15,16).…”

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confidence: 99%

Hyaluronan Synthase 2 (HAS2) Promotes Breast Cancer Cell Invasion by Suppression of Tissue Metalloproteinase Inhibitor 1 (TIMP-1)

Bernert

Porsch

Heldin

2011

Journal of Biological Chemistry

104

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Invasion and metastasis are the primary causes of breast cancer mortality, and increased knowledge about the molecular mechanisms involved in these processes is highly desirable. High levels of hyaluronan in breast tumors have been correlated with poor patient survival. The involvement of hyaluronan in the early invasive phase of a clone of breast cancer cell line MDA-MB-231 that forms bone metastases was studied using an in vivo-like basement membrane model. The metastatic to bone tumor cells exhibited a 7-fold higher hyaluronan-synthesizing capacity compared with MDA-MB-231 cells predominately due to an increased expression of hyaluronan synthase 2 (HAS2). We found that knockdown of HAS2 completely suppressed the invasive capability of these cells by the induction of tissue metalloproteinase inhibitor 1 (TIMP-1) and dephosphorylation of focal adhesion kinase. HAS2 knockdown-mediated inhibition of basement membrane remodeling was rescued by HAS2 overexpression, transfection with TIMP-1 siRNA, or addition of TIMP-1-blocking antibodies. Moreover, knockdown of HAS2 suppressed the EGF-mediated induction of the focal adhesion kinase/PI3K/Akt signaling pathway. Thus, this study provides new insights into a possible mechanism whereby HAS2 enhances breast cancer invasion.A hallmark of the malignant phenotype is acquisition of an invasive phenotype that allows cancer cells to degrade the basement membrane before they enter the circulation via blood or lymphatic vessels. The basement membrane is a specialized form of the extracellular matrix that underlies epithelial cells and surrounds blood vessels (1). Turnover of the basement membrane and extracellular matrix is regulated by the balance between metalloproteinases (MMPs) 2 and their naturally occurring tissue inhibitors of MMP (TIMPs). Up-regulation of MMPs or lack of TIMPs has been reported to be involved in cancer cell invasion (1-3). However, the relationship between MMPs and TIMPs is complex because both of them can be overexpressed in malignancies and be associated with tumorigenesis (4, 5). The MMP family of proteolytic enzymes consists of Ͼ20 secreted or membrane-anchored enzymes. MMP2, MMP7, and MMP9 are secreted as latent precursor forms (pro-MMP2, pro-MMP7, and pro-MMP9) that are activated at the cell surface and cleave collagen type IV, which is the principal structural constituent of the basement membrane. Membrane type 1 (MT1) MMP catalyzes the activation of pro-MMP2, which in turn activates pro-MMP9, propagating basement membrane proteolysis (1, 2, 6, 7). MMPs can localize transiently to the plasma membrane and become activated through their interactions with adhesion molecules, such as CD44 (8 -10).Accumulating evidence has demonstrated that CD44 and its ligand hyaluronan, a core component of the extracellular matrix, contribute to the invasive behavior and progression of multiple cancers. CD44 exists in various isoforms, the standard form (CD44s) and the variant forms (CD44v1-10), all of which can bind hyaluronan (11-14). Increased hyaluronan synthesis...

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Involvement of CD44, a molecule with a thousand faces, in cancer dissemination

Cited by 261 publications

References 56 publications

Silencing of CD44 by siRNA suppressed invasion, migration and adhesion to matrix, but not secretion of MMPs, of cholangiocarcinoma cells

Silencing of CD44 by siRNA suppressed invasion, migration and adhesion to matrix, but not secretion of MMPs, of cholangiocarcinoma cells

Quinoline based mono- and bis-(thio)carbohydrazones: synthesis, anticancer activity in 2D and 3D cancer and cancer stem cell models

Hyaluronan Synthase 2 (HAS2) Promotes Breast Cancer Cell Invasion by Suppression of Tissue Metalloproteinase Inhibitor 1 (TIMP-1)

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