Cathepsin B defines leader cells during the collective invasion of salivary adenoid cystic carcinoma

Wu, Jian; Li, Zhu-Feng; Wang, Haofan; Yu, Xixun; Pang, Xin; Wang, Shasha; Zhang, Mei; Yang, Xiao; Cao, Mingxin; Tang, Ya‐Jie; Liang, Xin‐hua; Zheng, Min; Tang, Yaling

doi:10.3892/ijo.2019.4722

Cited by 22 publications

(30 citation statements)

References 60 publications

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“…In another study, oncogenic mutations in CDKN2A, KRAS, TP53, and SMAD4 introduced into human pancreatic organoids transformed normal cells into cancer cells, modelling primary and invasive pancreatic ductal adenocarcinoma when xenotransplanted in vivo [163]. Cancer organoids have also been used to model metastatic processes, in particular to investigate the different processes of invasion [164,165]. For example, a study conducted on CRC organoids showed that inhibition of rho-associated protein kinase 2 (ROCK2) improved collective invasion in its early stages [166].…”

Section: Organoids As a Model To Study Tumorigenesismentioning

confidence: 99%

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Modeling neoplastic disease with spheroids and organoids

et al. 2020

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Cancer is a complex disease in which both genetic defects and microenvironmental components contribute to the development, progression, and metastasization of disease, representing major hurdles in the identification of more effective and safer treatment regimens for patients. Three-dimensional (3D) models are changing the paradigm of preclinical cancer research as they more closely resemble the complex tissue environment and architecture found in clinical tumors than in bidimensional (2D) cell cultures. Among 3D models, spheroids and organoids represent the most versatile and promising models in that they are capable of recapitulating the heterogeneity and pathophysiology of human cancers and of filling the gap between conventional 2D in vitro testing and animal models. Such 3D systems represent a powerful tool for studying cancer biology, enabling us to model the dynamic evolution of neoplastic disease from the early stages to metastatic dissemination and the interactions with the microenvironment. Spheroids and organoids have recently been used in the field of drug discovery and personalized medicine. The combined use of 3D models could potentially improve the robustness and reliability of preclinical research data, reducing the need for animal testing and favoring their transition to clinical practice. In this review, we summarize the recent advances in the use of these 3D systems for cancer modeling, focusing on their innovative translational applications, looking at future challenges, and comparing them with most widely used animal models.

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Section: Organoids As a Model To Study Tumorigenesismentioning

confidence: 99%

“…Cancer organoids have also been used to model metastatic processes, in particular to investigate the different processes of invasion [ 164 , 165 ]. For example, a study conducted on CRC organoids showed that inhibition of rho-associated protein kinase 2 (ROCK2) improved collective invasion in its early stages [ 166 ].…”

Section: Organoid Modelmentioning

confidence: 99%

Modeling neoplastic disease with spheroids and organoids

et al. 2020

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“…This state of co-existence for epithelial and mesenchymal traits in a single cell is more favorable for collective cell movement compared to complete mesenchymal phenotypes [ 29 ]. In salivary adenoid cystic carcinoma, cancer cells at the invasion front preserve the expression of epithelial marker E-cadherin and also express mesenchymal markers, N-cadherin and vimentin, suggesting that leader cells at the invasion front gain an incomplete EMT phenotype [ 92 ]. Similarly, Konen et al used a spatiotemporal genomic and cellular analysis technique to purify leader and follower cell lines and found that leader cells showed increased staining of the mesenchymal protein vimentin but decreased expression of N-cadherin, thereby indicating a partial EMT in leader cells [ 93 ].…”

Section: Plasticity Of Cancer Invasion Modesmentioning

confidence: 99%

Plasticity of cancer cell invasion: Patterns and mechanisms

Jiang

Chen

et al. 2021

Translational Oncology

131

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Cancer cell migration and invasion are integral components of metastatic disease, which is the major cause of death in cancer patients. Cancer cells can disseminate and migrate via several alternative mechanisms including amoeboid cell migration, mesenchymal cell migration, and collective cell migration. These diverse movement strategies display certain specific and distinct hallmarks in cell-cell junctions, actin cytoskeleton, matrix adhesion, and protease activity. During tumor progression, cells pass through complex microenvironments and adapt their migration strategies by reversible mesenchymal-amoeboid and individual-collective transitions. This plasticity in motility patterns enables cancer cells disseminate further and thus limit the efficiency of anti-metastasis therapies. In this review, we discuss the modes and mechanisms of cancer cell migration and focus on the plasticity of tumor cell movement as well as potential emerging therapeutic options for reducing cancer cell invasion.

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“…Furthermore, Cathepsin B has been found to involve in the progression of cancer in human in aspects of capase dependent apoptosis and in the processes of facilitating tumour neovascularization and metastasis (Mijanovic, 2019). Moreover, Cathepsin B was also found to be involved in cancer metastasis by making alterations in the extracellular matrix remodeling and facilitating invasion in different tissues of the body 42 . Such considerations provoke the fact that research related to investigating the most specific inhibitor for Cathepsin B needs to be encouraged and such studies could be facilitated very easily when recombinant production of Cathepsin B is made available.…”

Section: Main Textmentioning

confidence: 99%

A Review on Molecular Functional and Structural Characterization of Human Cysteine Cathepsins in Bacterial Expression Systems

Cooray¹,

Madubashetha²,

Warnakula³

et al. 2019

Preprint

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Cysteine cathepsins, a class of proteinaceous enzymes, regulate a wide variety of metabolic processes in human including protein breakdown and turnover and immune functions. Eleven cysteine cathepsins have been identified so far and a wide array of studies related to identifying their specific functions, regulation and distribution patterns in tissues have been conducted.However, in recent past, the association of cysteine cathepsins in occurrence and progression of cancers have been identified and this has caused unrest in scientists triggering them to investigate the physiology, biochemical pathways and interactions of these cathepsins in cancer metastasis and therefore has become a noteworthy topic of intensive research. This review focusses and collects together the published work on molecular functional and structural characterization studies that have been done so far on in vitro expression of genes encoding for cysteine cathepsins in the Escherichia coli bacterial expression system. Accordingly, it was found out that all cathepsins except for cathepsins K, C, H, X and W have been expressed this way and the majority of them were found to be expressed in E. coli BL21(DE3) pLysS expression host via pET3 expression vector. In addition, it was also noted that in most of the expression studies, the substrate that was used to validate the enzymatic activity of the recombinant enzyme that was produced was a cysteine residue along with a benzyloxy-carbonyl salt. Through this review, the authors suggest that there is a very high need that all cysteine cathepsins need to be characterized both structurally and functionally on a molecular platform to better understand their interactions including the biochemical pathways. It is also momentous that the mass production of the recombinant forms of these enzymes are facilitated via expression in such bacterial expression systems and in turn, would also provide a strong platform for the development and progression of studies related to human physiology including oncological studies such as cancer metastasis. Moreover, as per biochemical features of the enzymes that could be identified, the production of efficient inhibitors or inducers as per the necessity to improve health and promote wellbeing among the mankind could be facilitated.

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Cathepsin B defines leader cells during the collective invasion of salivary adenoid cystic carcinoma

Cited by 22 publications

References 60 publications

Modeling neoplastic disease with spheroids and organoids

Modeling neoplastic disease with spheroids and organoids

Plasticity of cancer cell invasion: Patterns and mechanisms

A Review on Molecular Functional and Structural Characterization of Human Cysteine Cathepsins in Bacterial Expression Systems

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