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Meeting ReportEducational Exhibits - Oncology

Cancer associated fibroblasts: Beyond the basics

Fereshteh Yazdanpanah, Eric Teichner, Robert Subtirelu, Michael Morris, Mona-Elisabeth Revheim, Thomas Werner, Abass Alavi and Babak Saboury
Journal of Nuclear Medicine June 2023, 64 (supplement 1) P1538;
Fereshteh Yazdanpanah
1Hospital of University of Pennsylvania
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Eric Teichner
2University of Pennsylvania
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Robert Subtirelu
2University of Pennsylvania
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Michael Morris
3National Institutes Health
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Mona-Elisabeth Revheim
4Oslo University Hospital and University of Oslo
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Thomas Werner
5Hospital of the University of Pennsylvania
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Abass Alavi
2University of Pennsylvania
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Babak Saboury
6National Institutes of Health (NIH) - Clinical Center
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Abstract

P1538

Introduction:

1. Examine the role of cancer-associated fibroblasts (CAFs) in the survival, maturation, and progression of cancer cells. 2. Discuss the heterogeneity of CAFs, including the various subsets present in different types of cancer and their potential tumor-promoting or tumor-suppressive effects. 3. Determine the utility of metabolic information in the determination of CAF invasion and migration.

Methods:

PubMed, Scopus, Web of Science were utilized in order assess trends in the existing literature. Articles that examined the role of cancer-associated fibroblasts (CAFs) in the progression of cancer were analyzed. Data regarding study design, sample size, radioligands, and conclusions drawn were extracted from the relevant research. Limitations and potential areas for future investigation were identified. The results of these studies were synthesized to address the objectives and clarify the role of CAFs in cancer biology.

Results:

Stromal fibroblast cells are converted to cancer-associated fibroblasts (CAFs) by tumor cells via the stimulation of paracrine growth factors. CAFs are more productive than regular stromal fibroblasts in maintaining cell survival and promoting maturation. CAFs secrete several growth factors, including transforming growth factor-b1 (a potent extracellular signal controlling Epithelial–mesenchymal transition (EMT)) (1). CAFs also secrete chemokine (C-X-C motif) ligand 12 (CXCL12)/stromal derived factor1 (SDF-1) to promote EMT. Epithelial–mesenchymal transition (EMT) is a reversible cellular program that transiently sets epithelial cells into quasi-mesenchymal cell states by E-cadherin expression repression, which leads to the loss of the typical polygonal, cobblestone morphology of epithelial cells. CAFs promote the invasion and migration of cancer cells through extracellular matrix (ECM) remodeling by ECM-degrading proteases secreted from cancer cells with the EMT phenotype.

CAFs allow diverse cells within the tumor stroma to communicate with one another. Stromal fibroblast expansion with proliferation, which is termed "stromagenesis", is associated with tumorigenesis. CAFs are extremely heterogeneous and contain an assortment of provoked fibroblasts that can arise from quiet local fibroblasts, bone marrow-derived mesenchymal stem cells (BM-MSCs), tumor cells, endothelial cells, adipocytes, and stellate cells. CAFs have various subsets in different cancers, demonstrating their heterogenicity. For example, in breast cancer and within metastatic tumors within lymph nodes, there are four CAF subsets (CAF-S1–S4). There is no one biomarker to specifically recognize the entire CAF population. Biomarkers represented on triggered CAFs include: Platelet-derived growth factor receptor (PDGFR), α-smooth muscle actin (αSMA), and fibroblast activation protein (FAP). The literature indicates that αSMA and FAP allow for the categorization of specific CAF subpopulations. Generally, PDGFR is co-expressed with αSMA and characterizes a subset of αSMA+ CAFs. The presence of αSMA+ CAFs are associated with worse outcomes. It follows that αSMA+ fibroblasts are protumorigenic subtypes. Considerable studies have disclosed that CAFs have distinguished roles in cancer pathogenesis, which has extensive clinical implications. CAFs construct and recondition the extracellular matrix (ECM) arrangement, which facilitates the tumor cells' invasion and interaction with cancer cells or other stromal cells. FAP as one of the significant markers of CAF in malignant tissue stroma can be used for early tumor detection and profiling.

Conclusions:

CAFs are one the most abundant elements of tumor stroma that have important molecular markers, such as FAP. FAP inhibitor (FAPI) may become an important emerging radiotracer in PET imaging. An understanding of the characteristics of CAF can inform clinicians’ evaluation of FAPI PET.

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Journal of Nuclear Medicine
Vol. 64, Issue supplement 1
June 1, 2023
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Cancer associated fibroblasts: Beyond the basics
Fereshteh Yazdanpanah, Eric Teichner, Robert Subtirelu, Michael Morris, Mona-Elisabeth Revheim, Thomas Werner, Abass Alavi, Babak Saboury
Journal of Nuclear Medicine Jun 2023, 64 (supplement 1) P1538;

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Cancer associated fibroblasts: Beyond the basics
Fereshteh Yazdanpanah, Eric Teichner, Robert Subtirelu, Michael Morris, Mona-Elisabeth Revheim, Thomas Werner, Abass Alavi, Babak Saboury
Journal of Nuclear Medicine Jun 2023, 64 (supplement 1) P1538;
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