A new editorial perspective was published in Oncotarget's Volume 14 on March 21, 2023, entitled, “Cancer-associated fibroblasts: challenges and opportunities.”

Cancer-associated fibroblasts (CAFs) are a type of cell that plays a key role in the tumor microenvironment. While these cells have been extensively studied, their precise role in cancer development and progression is still not fully understood. 

In this new editorial perspective, researchers Hossein Tavana and Gary D. Luker from The University of Akron and the University of Michigan provide a comprehensive overview of CAFs, including the origins, characteristics, heterogeneity, and functions of CAFs, as well as CAFs in the detection and treatment of cancer.

The authors suggest that a deeper understanding of cancer-associated fibroblasts is crucial for the development of effective cancer therapies. They note that these cells are involved in a variety of important processes, including tumor growth, angiogenesis and immune evasion. However, targeting cancer-associated fibroblasts has proven to be a challenging task, in part because of their complex and multifaceted nature.

Despite these challenges, the researchers are optimistic about the future of research into CAFs. They note a number of studies targeting cancer-associated fibroblasts in emerging therapies. The authors conclude by emphasizing that a deeper understanding of cancer-associated fibroblasts and the tumor microenvironment could ultimately lead to the development of personalized therapies that are tailored to the unique characteristics of each patient's cancer.

“Delineating cross-talk of CAFs with cancer cells and other stromal cells, uncovering the role of CAFs in resistance to chemotherapies and immunotherapies, addressing challenges associated with CAFs heterogeneity to develop CAFs subtype-targeted therapies in the context of specific tumor types, and addressing the potential toxicity of such therapies especially when combined with other treatments will expedite the ongoing efforts for the translation of therapies against CAFs.”

Editorial perspective: DOI: https://doi.org/10.18632/oncotarget.28385 

Correspondence to: Hossein Tavana - tavana@uakron.edu 

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Keywords - fibroblasts, cancer-associated fibroblasts, tumor microenvironment, therapeutic targeting

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Oncotarget

Cancer-Associated Fibroblasts: Challenges and Opportunities

A new research perspective was published in Oncotarget's Volume 14 on April 26, 2023, entitled, “Disruption of retinol-mediated IL-6 expression in colon cancer-associated fibroblasts: new perspectives on the role of vitamin A metabolism.”

Colon cancer (CRC) is one of the most common malignancies and is a leading cause of cancer-related deaths worldwide. While the tumor microenvironment (TME) supports tumor growth and immune escape through tumor-promoting inflammation, the mechanisms by which the TME promotes CRC are far from being elucidated. Stromal myo-/fibroblasts (MFs) account for up to 30% of lamina propria cells in the normal human colon and their number is dramatically increased in CRC. 

Fibroblasts from cancers, also known as cancer-associated fibroblasts (CAFs), differ from normal colonic MF (N-MFs) and support tumor-promoting inflammation, in part due to increased IL-6 secretion. CAFs are very abundant in the TME and are among the major cells involved in tumor inflammation and progression. In this research perspective, researchers Romain Villéger, Marina Chulkina, Randy C. Mifflin, Don W. Powell, and Irina V. Pinchuk from the Université de Poitiers, Penn State Health Milton S. Hershey Medical Center and The University of Texas Medical Branch highlight recent data obtained regarding IL-6 regulation in colorectal cancer CAFs through vitamin A (retinol) metabolism, discuss current limitations in our understanding of the mechanisms leading to the CAF pro-inflammatory phenotype, and discuss potential approaches to target CAF retinoid metabolism during CRC treatment.

"While the overall mechanisms responsible for the IL-6 increase within the CRC tumor stroma remain to be elucidated, our study highlights the crucial role of stromal vitamin A pathway in IL-6 regulation."

DOI: https://doi.org/10.18632/oncotarget.28399

Correspondence to - Iryna V. Pinchuk - ipinchuk@pennstatehealth.psu.edu

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Keywords - tumor microenvironment, colon cancer, inflammation, fibroblasts, IL-6

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Retinol Disruption and The Role of Vitamin A Metabolism in Colon Cancer

Dr. Gopal C. Kundu from KIIT Deemed to be University in Odisha, India, describes a recent editorial he co-authored that was published by Oncotarget in Volume 14, entitled, “The molecular dialogue between the tumor cells and fibroblasts.”

DOI - https://doi.org/10.18632/oncotarget.28405

Correspondence to - Gopal C. Kundu - gopalc.kundu@kiit.ac.in

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Keywords - CAFs, heterogeneity, myofibroblasts, drug resistance, osteopontin

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Behind the Study: Molecular Dialogue Between Tumor Cells and Fibroblasts

A new research paper was published on the cover of Aging (Aging-US) Volume 15, Issue 14, entitled, “Human senescent fibroblasts trigger progressive lung fibrosis in mice.”

Cell senescence has recently emerged as a potentially relevant pathogenic mechanism in fibrosing interstitial lung diseases (f-ILDs), particularly in idiopathic pulmonary fibrosis. In a new study, researchers Fernanda Hernandez-Gonzalez, Neus Prats, Valentina Ramponi, José Alberto López-Domínguez, Kathleen Meyer, Mònica Aguilera, María Isabel Muñoz Martín, Daniel Martínez, Alvar Agusti, Rosa Faner, Jacobo Sellarés, Federico Pietrocola, and Manuel Serrano from Hospital Clinic Barcelona, The Barcelona Institute of Science and Technology (BIST), Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of Barcelona, Karolinska Institute, Catalan Institution for Research and Advanced Studies (ICREA), and Altos Labs hypothesized that senescent human fibroblasts may suffice to trigger a progressive fibrogenic reaction in the lung. 

“Here we: (1) explored this hypothesis in vivo; (2) investigated the potential underlying biological mechanisms in vitro; and (3) studied the effects of one experimental senolytic compound (navitoclax) and two anti-fibrotic drugs currently used in the treatment of IPF in humans (nintedanib and pirfenidone), both in vivo and in vitro.”

To address this, senescent human lung fibroblasts, or their secretome (SASP), were instilled into the lungs of immunodeficient mice. The researchers found that human senescent fibroblasts engraft in the lungs of immunodeficient mice and trigger progressive lung fibrosis associated to increasing levels of mouse senescent cells, whereas non-senescent fibroblasts do not trigger fibrosis. They also found that the SASP of human senescent fibroblasts is pro-senescence and pro-fibrotic both in vitro when added to mouse recipient cells and in vivo when delivered into the lungs of mice, whereas the conditioned medium (CM) from non-senescent fibroblasts lacks these activities. Finally, navitoclax, nintedanib and pirfenidone were found to ameliorate lung fibrosis induced by senescent human fibroblasts in mice, while only navitoclax displayed senolytic activity. 

“We conclude that human senescent fibroblasts, through their bioactive secretome, trigger a progressive fibrogenic reaction in the lungs of immunodeficient mice that includes the induction of paracrine senescence in the cells of the host, supporting the concept that senescent cells actively contribute to disease progression in patients with f-ILDs.”

DOI - https://doi.org/10.18632/aging.204825

Corresponding authors - Manuel Serrano - mserrano@altoslabs.com, and Federico Pietrocola - federico.pietrocola@ki.se

Keywords - aging, mouse model, cellular senescence, pulmonary fibrosis, antifibrotics, senolytic

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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Aging (Aging-US)

Human Senescent Fibroblasts Cause Lung Fibrosis in Mice

Creative Bioarray cDNA is synthesized from a highly pure and intact total RNA.

https://www.creative-bioarray.com/Skin-Fibroblast-cDNA-AVM-CSC-CD-AVM-item-40865.htm

Fibroblasts

BUFFALO, NY — September 18, 2025 — A new #research paper was #published  in Volume 17, Issue 8 of Aging-US on August 9, 2025, titled “The myokine FGF21 associates with enhanced survival in ALS and mitigates stress-induced cytotoxicity.”

In this study, led by first author Abhishek Guha and corresponding author Peter H. King from the University of Alabama at Birmingham and the Birmingham Veterans Affairs Medical Center, researchers discovered that a hormone called FGF21, which is released by muscles, is elevated in people with amyotrophic lateral sclerosis (ALS) and may play a protective role. These findings are especially relevant because ALS is a fatal and currently incurable neurodegenerative disease.

Amyotrophic lateral sclerosis is an age-related and progressive condition that affects the nerve cells responsible for muscle control. While some treatments can slow the disease, there is still a need to understand why ALS progresses at different rates in different individuals.

“In a prior muscle miRNA sequencing investigation, we identified altered FGF pathways in ALS muscle, leading us to investigate FGF21.”

The research team analyzed muscle biopsies, spinal cord tissue, and blood samples from ALS patients and found that FGF21 levels were significantly elevated. This increase was particularly evident in atrophied muscle fibers—those that had shrunk due to nerve loss—and in the surrounding tissue. Importantly, patients with higher plasma levels of FGF21 showed slower loss of function and longer survival, with some living more than six years after diagnosis.

Using animal models and cultured cells, the researchers demonstrated that FGF21 levels rise even in the early, symptom-free stages of ALS. The hormone appeared to protect both muscle and motor neurons from stress-related damage. When added to stressed cells, FGF21 improved cell survival and reduced markers of cell death. In human muscle cells, FGF21 also supported the formation of new muscle fibers, a process known as myogenesis.

Blood tests revealed that patients with higher levels of FGF21 not only experienced slower disease progression but also tended to have a higher body mass index (BMI), a factor previously associated with longer survival in ALS. This suggests that FGF21 may reflect a patient’s ability to counteract ALS through natural protective mechanisms. It could also serve as a biomarker to monitor disease severity and potentially guide treatment decisions.

The study also investigated how FGF21 communicates with cells. It found that the hormone’s activity depends on a protein called β-Klotho, which was also altered in ALS-affected tissues. These changes were especially noticeable in motor neurons and muscle cells under stress, further highlighting FGF21’s role in the body’s response to damage.

While the study does not show that FGF21 can be used as a treatment, it highlights the hormone as a promising target for future research, clinical trials, and strategies to slow ALS progression by leveraging the body’s natural protective systems.

DOI - https://doi.org/10.18632/aging.206298

Corresponding author - Peter H. King - phking@uabmc.edu

Abstract video - https://www.youtube.com/watch?v=zEGMxQrxZxE

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Keywords - aging, fibroblast growth factor, 21 β-Klotho, ALS biomarker, human skeletal muscle, motor neurons

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Aging-US

FGF21 Muscle Hormone Associated with Slow ALS Progression and Extended Survival

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Oncotarget is now indexed by MEDLINE, PubMed and PMC/PubMed.

Read about the Oncotarget Scientific Integrity Process: https://www.oncotarget.com/scientific_integrity/

Aging-US is dedicated to advancing our understanding of the biological mechanisms that drive aging and the development of age-related diseases. Our mission is to serve as a platform for high-quality research that uncovers the cellular, molecular, and systemic processes underlying aging, and translates these insights into strategies to extend healthspan and delay the onset of chronic disease.

Read about the Aging (Aging-US) Scientific Integrity Process: https://aging-us.com/scientific-integrity

New tracks tagged #Fibroblasts