Fibroblast activation protein

Li, Rui; Li, Hui; Liu, Liang; Yu, Jinpu; Ren, Xiaoyan

doi:10.4161/cbt.13.3.18696

Cited by 143 publications

(72 citation statements)

References 61 publications

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“…In addition to matrix deposition, matrix remodeling is an important aspect of a pro-tumorigenic microenvironment, acting to promote growth factor release, tumor vascularization, and migratory and invasive capacities of tumor cells, all of which can promote tumor cell metastasis. Factors known to play a role in this process include MMPs [5,31] and FAP, a membrane-bound serine protease that is thought to be selectively expressed by CAFs from tumors of epithelial origin [66]. In the present study, data show mRNA expression of FAP and production of active MMPs by HSC-CAFs.…”

Section: Discussionsupporting

confidence: 58%

Hematopoietic Stem Cell–Derived Cancer–Associated Fibroblasts Are Novel Contributors to the Pro-Tumorigenic Microenvironment

et al. 2015

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Targeting the tumor microenvironment is critical toward improving the effectiveness of cancer therapeutics. Cancer-associated fibroblasts (CAFs) are one of the most abundant cell types of the tumor microenvironment, playing an important role in tumor progression. Multiple origins for CAFs have been proposed including resident fibroblasts, adipocytes, and bone marrow. Our laboratory previously identified a novel hematopoietic stem cell (HSC) origin for CAFs; however, the functional roles of HSC-derived CAFs (HSC-CAFs) in tumor progression have not yet been examined. To test the hypothesis that HSC-CAFs promote tumor progression through contribution to extracellular matrix (ECM) and paracrine production of pro-angiogenic factors, we developed a method to isolate HSC-CAFs. HSC-CAFs were profiled on the basis of their expression of hematopoietic and fibroblastic markers in two murine tumor models. Profiling revealed production of factors associated with ECM deposition and remodeling. Functional in vivo studies showed that co-injection of HSC-CAFs with tumor cells resulted in increased tumor growth rate and significantly larger tumors than tumor cells alone. Immunohistochemical studies revealed increased blood vessel density with co-injection, demonstrating a role for HSC-CAFs in tumor vascularization. Mechanistic in vitro studies indicated that HSC-CAFs play a role in producing vascular endothelial growth factor A and transforming growth factor–β1 in endothelial tube formation and patterning. In vitro and in vivo findings suggest that HSC-CAFs are a critical component of the tumor microenvironment and suggest that targeting the novel HSC-CAF may be a promising therapeutic strategy.

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Section: Discussionsupporting

confidence: 58%

Hematopoietic Stem Cell–Derived Cancer–Associated Fibroblasts Are Novel Contributors to the Pro-Tumorigenic Microenvironment

et al. 2015

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“…FAP is a major focus for targeted therapy of stromal cells 297 . In the late 1990s and early 2000s, the anti-FAP monoclonal antibody F19 was tested in clinical trials for the treatment and imaging (via 131 I–mAbF19) of colorectal tumours but failed to impart a clinical benefit, likely because the antibodies used did not mediate antibody-dependent cellular toxicity of FAP-expressing stromal cells 298–301 .…”

Section: Tumour-stroma Targeting Strategiesmentioning

confidence: 99%

Targeting the tumour stroma to improve cancer therapy

2018

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Cancers are not merely composed of cancer cells alone and, instead, are complex ‘ecosystems’ comprising many different cell types and noncellular factors. The tumour stroma is a critical component of the tumour microenvironment, where it has crucial roles in tumour initiation, progression, and metastasis. Most anticancer therapies target cancer cells specifically, but the tumour stroma can promote resistance of cancer cells to such therapies, eventually resulting in fatal disease. Therefore, novel treatment strategies should combine anticancer and antistroma agents. Herein, we provide an overview of the advances in understanding the complex cancer cell–tumour stroma interactions, and discuss how this knowledge can result in more effective therapeutic strategies, which might ultimately improve patient outcomes.

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“…However, it has been reported that FAP can also function as a tumor suppressor [11]. These findings would suggest that FAP can show different functional behavior depending on the surrounding microenvironment [11,12]. Furthermore, FAP is expressed on several tumor cells and thus it is difficult to define the relative contribution of MSC and neoplastic cells to TME due to this enzyme [11,12].…”

Section: Msc Phenotypic and Functional Features Relevant In The Inmentioning

confidence: 99%

Mesenchymal Stromal Cells Can Regulate the Immune Response in the Tumor Microenvironment

Poggi

Giuliani

2016

Vaccines

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The tumor microenvironment is a good target for therapy in solid tumors and hematological malignancies. Indeed, solid tumor cells’ growth and expansion can influence neighboring cells’ behavior, leading to a modulation of mesenchymal stromal cell (MSC) activities and remodeling of extracellular matrix components. This leads to an altered microenvironment, where reparative mechanisms, in the presence of sub-acute inflammation, are not able to reconstitute healthy tissue. Carcinoma cells can undergo epithelial mesenchymal transition (EMT), a key step to generate metastasis; these mesenchymal-like cells display the functional behavior of MSC. Furthermore, MSC can support the survival and growth of leukemic cells within bone marrow participating in the leukemic cell niche. Notably, MSC can inhibit the anti-tumor immune response through either carcinoma-associated fibroblasts or bone marrow stromal cells. Experimental data have indicated their relevance in regulating cytolytic effector lymphocytes of the innate and adaptive arms of the immune system. Herein, we will discuss some of the evidence in hematological malignancies and solid tumors. In particular, we will focus our attention on the means by which it is conceivable to inhibit MSC-mediated immune suppression and trigger anti-tumor innate immunity.

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Fibroblast activation protein

Cited by 143 publications

References 61 publications

Hematopoietic Stem Cell–Derived Cancer–Associated Fibroblasts Are Novel Contributors to the Pro-Tumorigenic Microenvironment

Hematopoietic Stem Cell–Derived Cancer–Associated Fibroblasts Are Novel Contributors to the Pro-Tumorigenic Microenvironment

Targeting the tumour stroma to improve cancer therapy

Mesenchymal Stromal Cells Can Regulate the Immune Response in the Tumor Microenvironment

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