The Role of Cancer-Associated Fibroblasts in Cancer Invasion and Metastasis

Asif, Paris Jabeen; Longobardi, Ciro; Hahne, Michael; Medema, Jan Paul

doi:10.3390/cancers13184720

Cited by 143 publications

(108 citation statements)

References 147 publications

(182 reference statements)

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“…The degradation of the ECM is considered an important marker of the progress of metastasis [13,14,[44][45][46]. Numerous previous studies have revealed that this process is catalyzed by proteins secreted by cancer cells and allows cancer cells to migrate to other tissues or organs [17].…”

Section: Discussionmentioning

confidence: 99%

The Inhibitory Effects of Terminalia catappa L. Extract on the Migration and Invasion of Human Glioblastoma Multiforme Cells

Chung

Hsieh

et al. 2021

Pharmaceuticals

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Glioblastoma multiforme (GBM) is one of the most aggressive and common types of brain tumor. Due to its high proliferation ability, a high lethality rate has been observed with this malignant glial tumor. Terminalia catappa L. (T. catappa) is currently known to have anti-inflammatory and anti-carcinogenesis effects. However, few studies have examined the mechanisms of the leaf extracts of T. catappa (TCE) on GBM cells. In the current study, we demonstrated that TCE can significantly inhibit the migration and invasion capabilities of GBM cell lines without showing biotoxic effects. Matrix metalloproteinases-2 (MMP-2) activity and protein expression were attenuated by reducing the p38 phosphorylation involved in the mitogen-activated protein kinase (MAPK) pathway. By treating with TCE and/or p38 inhibitor (SB203580), we confirmed that p38 MAPK is involved in the inhibition of cell migration. In conclusion, our results demonstrated that TCE inhibits human GBM cell migration and MMP-2 expression by regulating the p38 pathway. These results reveal that TCE contains potent therapeutic compounds which could be applied for treating GBM brain tumors.

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Section: Discussionmentioning

confidence: 99%

The Inhibitory Effects of Terminalia catappa L. Extract on the Migration and Invasion of Human Glioblastoma Multiforme Cells

Chung

Hsieh

et al. 2021

Pharmaceuticals

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“…As shown above, CAFs contribute a variety of growth factors to the TME, mediated in part by integrins, and facilitated by cadherins. CAFs are the proposed initiators of EMT in bladder cancer ( Goulet et al, 2019 ) and colorectal cancer ( Asif et al, 2021 ), and this extends to many other cancers, as well ( Fiori et al, 2019 ; Mezawa and Orimo, 2021 ). Taken together, this data suggests a fundamental role for CAFs in the epithelial-mesenchymal cooperation we propose.…”

Section: Cell-cell (E-cadherin Cdh1) and Cell-ecm (α6 Integrin Cd49f)...mentioning

confidence: 94%

Integrins and Epithelial-Mesenchymal Cooperation in the Tumor Microenvironment of Muscle-Invasive Lethal Cancers

Harryman

Marr

Nagle

et al. 2022

Front. Cell Dev. Biol.

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Muscle-invasive lethal carcinomas traverse into and through this specialized biophysical and growth factor enriched microenvironment. We will highlight cancers that originate in organs surrounded by smooth muscle, which presents a barrier to dissemination, including prostate, bladder, esophageal, gastric, and colorectal cancers. We propose that the heterogeneity of cell-cell and cell-ECM adhesion receptors is an important driver of aggressive tumor networks with functional consequences for progression. Phenotype heterogeneity of the tumor provides a biophysical advantage for tumor network invasion through the tensile muscle and survival of the tumor network. We hypothesize that a functional epithelial-mesenchymal cooperation (EMC)exists within the tumor invasive network to facilitate tumor escape from the primary organ, invasion and traversing of muscle, and navigation to metastatic sites. Cooperation between specific epithelial cells within the tumor and stromal (mesenchymal) cells interacting with the tumor is illustrated using the examples of laminin-binding adhesion molecules—especially integrins—and their response to growth and inflammatory factors in the tumor microenvironment. The cooperation between cell-cell (E-cadherin, CDH1) and cell-ECM (α6 integrin, CD49f) expression and growth factor receptors is highlighted within poorly differentiated human tumors associated with aggressive disease. Cancer-associated fibroblasts are examined for their role in the tumor microenvironment in generating and organizing various growth factors. Cellular structural proteins are potential utility markers for future spatial profiling studies. We also examine the special characteristics of the smooth muscle microenvironment and how invasion by a primary tumor can alter this environment and contribute to tumor escape via cooperation between epithelial and stromal cells. This cooperative state allows the heterogenous tumor clusters to be shaped by various growth factors, co-opt or evade immune system response, adapt from hypoxic to normoxic conditions, adjust to varying energy sources, and survive radiation and chemotherapeutic interventions. Understanding the epithelial-mesenchymal cooperation in early tumor invasive networks holds potential for both identifying early biomarkers of the aggressive transition and identification of novel agents to prevent the epithelial-mesenchymal cooperation phenotype. Epithelial-mesenchymal cooperation is likely to unveil new tumor subtypes to aid in selection of appropriate therapeutic strategies.

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“…PDPN makes a complex with MMP14 and co-localizes at cell-surface protrusions, suggesting the potential of ECM destruction at sites [107]. In tumor cell invasion, not only tumor cells but also stromal cells express and secrete MMPs, which contributes to the destruction of the ECM for tumor invasion [108] (Figure 2). Furthermore, PDPN can stimulate TGF-β secretion in oral SCC cells, which activates surrounding fibroblasts, upregulating MMP2 and MMP14 expression [109].…”

Section: Cafmentioning

confidence: 99%

Roles of Podoplanin in Malignant Progression of Tumor

Suzuki

Kaneko

Kato

2022

Cells

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Podoplanin (PDPN) is a cell-surface mucin-like glycoprotein that plays a critical role in tumor development and normal development of the lung, kidney, and lymphatic vascular systems. PDPN is overexpressed in several tumors and is involved in their malignancy. PDPN induces platelet aggregation through binding to platelet receptor C-type lectin-like receptor 2. Furthermore, PDPN modulates signal transductions that regulate cell proliferation, differentiation, migration, invasion, epithelial-to-mesenchymal transition, and stemness, all of which are crucial for the malignant progression of tumor. In the tumor microenvironment (TME), PDPN expression is upregulated in the tumor stroma, including cancer-associated fibroblasts (CAFs) and immune cells. CAFs play significant roles in the extracellular matrix remodeling and the development of immunosuppressive TME. Additionally, PDPN functions as a co-inhibitory molecule on T cells, indicating its involvement with immune evasion. In this review, we describe the mechanistic basis and diverse roles of PDPN in the malignant progression of tumors and discuss the possibility of the clinical application of PDPN-targeted cancer therapy, including cancer-specific monoclonal antibodies, and chimeric antigen receptor T technologies.

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The Role of Cancer-Associated Fibroblasts in Cancer Invasion and Metastasis

Cited by 143 publications

References 147 publications

The Inhibitory Effects of Terminalia catappa L. Extract on the Migration and Invasion of Human Glioblastoma Multiforme Cells

The Inhibitory Effects of Terminalia catappa L. Extract on the Migration and Invasion of Human Glioblastoma Multiforme Cells

Integrins and Epithelial-Mesenchymal Cooperation in the Tumor Microenvironment of Muscle-Invasive Lethal Cancers

Roles of Podoplanin in Malignant Progression of Tumor

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