Article
Oncology
Mariam Oladejo, Hong-My Nguyen, Hannah Seah, Arani Datta, Laurence M. Wood
Summary: CD105 is a transmembrane protein highly expressed on endothelial cells, and contributes to tumor angiogenesis and progression. It is also expressed by tumor cells in certain cancers, such as renal cell carcinoma, where it is associated with stem cell-like properties. However, the role of tumor-expressed CD105 in the anti-tumor immune response and tumor microenvironment is still unclear.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Review
Oncology
Claudia Ollauri-Ibanez, Blanca Ayuso-inigo, Miguel Pericacho
Summary: The composition of the tumor microenvironment (TME) plays a crucial role in prognosis and response to immunotherapy. Cold tumors, with cells and molecules that inhibit antitumor response, have poor prognosis, while hot tumors, rich in antitumor cells, respond well to immunotherapy. Endoglin (CD105) is involved in angiogenesis, inflammation, and cancer-associated fibroblast (CAF) accumulation, making it a potential target for converting cold tumors into hot tumors.
Article
Pharmacology & Pharmacy
Qian Huang, Rui Xiao, Jing Lu, Yao Zhang, Liang Xu, Jie Gao, Jing Sun, Haiping Wang
Summary: This study revealed that endoglin exacerbated PF by regulating the activation of TGF-beta/ALK/Smads signaling, while its knockdown could alleviate peritoneal injury, providing a novel potential therapeutic target in PF.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Jeff Yat-Fai Chung, Max Kam-Kwan Chan, Jane Siu-Fan Li, Alex Siu-Wing Chan, Philip Chiu-Tsun Tang, Kam-Tong Leung, Ka-Fai To, Hui-Yao Lan, Patrick Ming-Kuen Tang
Summary: TGF-beta signaling plays crucial roles in inflammatory diseases by regulating immunocytes in tissue fibrosis and accelerating tumor development in cancer. The pleiotropic nature of TGF-beta signaling in generating fibrotic TME, containing CAFs and matrix proteins, remains largely unclear, despite recent studies demonstrating its clinical implications in cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Mariam Oladejo, Hong-My Nguyen, Laurence Wood
Summary: Molecular biomarkers interacting with vascular and immune compartments have a significant role in the progression of solid malignancies. CD105, a component of the TGF-β signaling cascade, has been extensively studied for its angiogenic role in various cancers. However, in renal cell carcinoma (RCC), CD105 has a diverse expression profile and multiple functions on tumor cells, tumor vasculature, and immune system components. This review summarizes the recent evidence and findings of the multifunctional roles of CD105 in angiogenesis and immunomodulation in different subtypes of RCC, with a specific emphasis on clear cell RCC. The review also provides an update on the preclinical and clinical applications of CD105 as a therapeutic platform in RCC.
Article
Genetics & Heredity
Arti Verma, Sandeep Artham, Payaningal R. Somanath
Summary: This study investigated the role of the Akt1 pathway in regulating ALK1 and ALK5 expression during TGF beta 1 and TGF beta 2-induced EndMT in human microvascular endothelial cells (HMECs). The findings demonstrated the significant impact of the Akt1 pathway on ALK1 and ALK5 expression, promoting EndMT.
Review
Oncology
Linwei Li, Qinglian Wen, Ruilin Ding
Summary: Normalizing the tumor microenvironment by inhibiting VEGF and TGF-beta pathways can enhance the effectiveness of immunotherapy. Clinical and preclinical evidence supports the use of anti-VEGF and/or anti-TGF-beta therapies as combination treatments with PD-(L)1 inhibitors for solid tumors. Further studies are needed to fully understand the clinical value of this approach.
FRONTIERS IN ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Teresa Gonzalez Munoz, Ana Teresa Amaral, Pilar Puerto-Camacho, Hector Peinado, Enrique de Alava
Summary: Endoglin has been identified as a potential disease biomarker and therapeutic target, playing various roles in physiological and pathological processes. It acts as a co-receptor in the TGF beta pathway and can also be released in soluble form to affect cell signaling. In cancer, endoglin may contribute to both oncogenic and non-oncogenic phenotypes, opening up possibilities for targeted therapies within the tumor microenvironment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Noam Cohen, Dhanashree Mundhe, Sarah K. Deasy, Omer Adler, Nour Ershaid, Tamar Shami, Oshrat Levi-Galibov, Rina Wassermann, Ruth Scherz-Shouval, Neta Erez
Summary: Metastatic cancer is difficult to cure and is the main cause of cancer-related deaths. In this study, the researchers found that cancer-associated fibroblasts play a crucial role in creating a favorable microenvironment for metastasis by mediating inflammation. They also discovered that a protein called Activin A is secreted from breast tumors and promotes fibrosis in the lung, which enhances metastasis. This new mechanism could potentially be targeted for therapeutic intervention to inhibit metastatic relapse.
Article
Nanoscience & Nanotechnology
Jun Zhang, Tiantian Zuo, Jie Yang, Zongwei Hu, Zhihua Wang, Rui Xu, Siyu Ma, Yawen Wei, Qi Shen
Summary: This study utilized bio-responsive nanoparticles to modulate the tumor microenvironment and successfully inhibited the formation of tumor-associated fibroblasts, reduced the secretion of transforming growth factor-β and collagen I.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Biochemistry & Molecular Biology
Tessa Gerrits, Isabella J. Brouwer, Kyra L. Dijkstra, Ron Wolterbeek, Jan A. Bruijn, Marion Scharpfenecker, Hans J. Baelde
Summary: Chronic kidney disease (CKD) involves progressive deterioration of renal function, characterized by glomerular sclerosis, tubular atrophy, and interstitial fibrosis. Endoglin, expressed in endothelial cells and fibroblasts, may function as a co-receptor of TGF signaling and potentially play a role in the progression of CKD. The study found that endoglin was upregulated in patients with CKD, particularly those with chronic allograft dysfunction and diabetic nephropathy. The overexpression of endoglin in human kidney fibroblasts also resulted in increased mRNA and protein upregulation of ECM components, suggesting its significance as a therapeutic target for the prevention of end-stage renal disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Rasmus S. Pedersen, Neel Nissen, Christina Jensen, Jeppe Thorlacius-Ussing, Tina Manon-Jensen, Majken L. Olesen, Lasse L. Langholm, Hadi M. H. Diab, Lars N. Jorgensen, Carsten P. Hansen, Inna M. Chen, Julia S. Johansen, Morten A. Karsdal, Nicholas Willumsen
Summary: This study aims to evaluate the cleavage of latency-associated protein (LAP) by plasma kallikrein (PLK) as a non-invasive biomarker for pancreatic ductal adenocarcinoma (PDAC) and tumor fibrosis. Preliminary results suggest that PLK-cleaved LAP-TGF-beta levels are elevated in PDAC patients and are associated with poor overall survival and tumor fibrosis.
Article
Biochemistry & Molecular Biology
Denis Belitskin, Shishir M. Pant, Pauliina Munne, Ilida Suleymanova, Kati Belitskina, Hanna-Ala Hongisto, Johanna Englund, Tiina Raatikainen, Olga Klezovitch, Valeri Vasioukhin, Shuo Li, Qingyu Wu, Outi Monni, Satu Kuure, Pirjo Laakkonen, Jeroen Pouwels, Topi A. Tervonen, Juha Klefstrom
Summary: This study demonstrates that hepsin, overexpressed in 70% of breast tumors, promotes canonical TGF beta signaling through a proteolytic downmodulation mechanism involving fibronectin in the mammary gland. Hepsin facilitates the release of latent-TGF beta from the ECM storage compartment, ultimately regulating the TGF beta pathway in mammary glands. This novel finding highlights hepsin's role as a regulator of TGF beta signaling in breast tumors via a unique mechanism.
Review
Oncology
Daniel R. Principe, Kaytlin E. Timbers, Luke G. Atia, Regina M. Koch, Ajay Rana
Summary: There is a lack of effective treatment for advanced PDAC patients, but TGF beta pathway inhibitors show promise in enhancing responses to current therapies. TGF beta signaling has complex roles in the pancreatic tumor microenvironment, with both tumor-suppressive and tumorigenic effects. Further research and clinical trials are ongoing to develop TGF beta inhibitors for the treatment of PDAC patients.
Review
Immunology
Baode Chen, Chenglin Mu, Zhiwei Zhang, Xuelin He, Xia Liu
Summary: Since its recognition as an essential cytokine in embryogenesis and tissue homeostasis, our understanding of the role of TGF-beta in mammalian development and disease, especially cancer, has been constantly updated. TGF-beta acts as the principal regulator of the immune system, but strengthening its signaling can limit immune response. The love-hate relationship between TGF-beta signaling and the immune system poses challenges in developing effective monotherapies, but recent studies on combination therapies have shown promising outcomes in cancer treatment.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Sarah Ouahoud, Rutger J. Jacobs, Ludmilla L. Kodach, Philip W. Voorneveld, Lukas J. A. C. Hawinkels, Nikki L. Weil, Britt van Vliet, Ron M. Herings, Lennart R. A. Van der Burg, Tom van Wezel, Hans Morreau, Marije Slingerland, Esther Bastiaannet, Hein Putter, James C. H. Hardwick
Summary: This study found that long-term use of statins is associated with a reduced risk of developing colorectal cancer, particularly for SMAD4-positive colorectal cancer.
BRITISH JOURNAL OF CANCER
(2022)
Article
Gastroenterology & Hepatology
Sumit Kumar, Mark J. A. Schoonderwoerd, Jessie S. Kroonen, Ilona J. de Graaf, Marjolein Sluijter, Dina Ruano, Roman Gonzalez-Prieto, Matty Verlaan-de Vries, Jasper Rip, Ramon Arens, Noel F. C. C. de Miranda, Lukas J. A. C. Hawinkels, Thorbald van Hall, Alfred C. O. Vertegaal
Summary: The pharmacological inhibition of the SUMO pathway represents a potential strategy for targeting PDAC by inhibiting cancer cell cycle progression and activating anti-tumor immunity through interferon signaling. TAK-981, a novel small molecule inhibitor, has shown potential in reducing SUMOylation and inhibiting the proliferation of PDAC cells.
Review
Biochemistry & Molecular Biology
Tom J. Harryvan, Sabine de Lange, Lukas J. A. C. Hawinkels, Els M. E. Verdegaal
Summary: In addition to professional antigen-presenting cells (APCs), nonprofessional APCs also play a role in presenting antigens to T cells, and their function has significant implications for immunotherapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Engineering, Biomedical
Niels Harlaar, Sven O. Dekker, Juan Zhang, Rebecca R. Snabel, Marieke W. Veldkamp, Arie O. Verkerk, Carla Cofino Fabres, Verena Schwach, Lente J. S. Lerink, Mathilde R. Rivaud, Aat A. Mulder, Willem E. Corver, Marie Jose T. H. Goumans, Dobromir Dobrev, Robert J. M. Klautz, Martin J. Schalij, Gert Jan C. Veenstra, Robert Passier, Thomas J. van Brakel, Daniel A. Pijnappels, Antoine A. F. de Vries
Summary: Functional human atrial myocytes can be massively expanded via a conditional cell-immortalization method, and used in in vitro models of atrial fibrillation. This study successfully generated immortalized cell lines with properties resembling primary atrial myocytes, and used them to create in vitro models of atrial fibrillation, displaying fibrillatory activity consistent with clinical manifestations and responding to antiarrhythmic drugs.
NATURE BIOMEDICAL ENGINEERING
(2022)
Article
Cardiac & Cardiovascular Systems
Alwin de Jong, Vincent Q. Sier, Hendrika A. B. Peters, Natalia K. M. Schilder, J. Wouter Jukema, Marie Jose T. H. Goumans, Paul H. A. Quax, Margreet R. de Vries
Summary: This study investigated the role of ALK1 signaling in vein graft disease, revealing that reduced ALK1 signaling promotes outward remodeling, increases macrophage influx, and promotes an unstable plaque phenotype in murine vein grafts.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Jessica Roelands, Manon Van der Ploeg, Marieke E. Ijsselsteijn, Hao Dang, Jurjen J. Boonstra, James C. H. Hardwick, Lukas J. A. C. Hawinkels, Hans Morreau, Noel F. C. C. de Miranda
Summary: Spatial profiling of pT1 CRC samples revealed the molecular and immunological landscape of early-stage colorectal cancer, identifying biomarkers associated with disease progression and targetable immune processes applicable in a clinical setting.
Review
Genetics & Heredity
Ilse Luyckx, Aline Verstraeten, Marie-Jose Goumans, Bart Loeys
Summary: This article reviews the clinical and genetic similarities of three diseases related to SMAD6, compares mouse models, and discusses the cellular mechanisms of SMAD6 in the development of these diseases. The importance of further research to improve molecular diagnosis, advance therapeutic strategies, and provide counseling for patients and their families is also emphasized.
NPJ GENOMIC MEDICINE
(2022)
Article
Engineering, Biomedical
Dylan Mostert, Bart Groenen, Leda Klouda, Robert Passier, Marie-Jose Goumans, Nicholas A. A. Kurniawan, Carlijn V. C. Bouten
Summary: In this study, the effect of ECM (dis)organization and cyclic strain on cardiomyocytes and cardiac fibroblasts (cFBs) was investigated in a two-dimensional human in vitro co-culture model of the myocardial microenvironment. The results showed that ECM protein patterning can guide cell orientation, and cFBs exhibit strain avoidance. However, cardiomyocytes only show strain avoidance when co-cultured with at least 30% cFBs via active remodeling of their sarcomeres.
APL BIOENGINEERING
(2022)
Review
Biochemistry & Molecular Biology
Imke Stouten, Nadine van Montfoort, Lukas J. A. C. Hawinkels
Summary: The lack of response to therapy in pancreatic ductal adenocarcinoma (PDAC) patients has led to PDAC having a low survival rate. Immunotherapy has shown promise in other cancer types but is ineffective in PDAC due to its unique tumor microenvironment (TME) with low immune activity. Cancer-associated fibroblasts (CAFs) in the TME may play a role in the low immunotherapy response. Understanding the interactions between CAFs and immune cells in the TME could improve immunotherapy for PDAC and similar cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Laura F. Ouboter, Marieke C. Barnhoorn, Hein W. Verspaget, Leonie Plug, Emma S. Pool, Karoly Szuhai, Lukas J. A. C. Hawinkels, Melissa van Pel, Jaap Jan Zwaginga, Dave Roelen, Frits Koning, M. Fernanda Pascutti, Andrea E. van der Meulen-de Jong
Summary: A phase IIa clinical study evaluated the impact of local mesenchymal stromal cell (MSC) therapy on ulcerative proctitis (UP), and found it to be safe, feasible, and showed encouraging signs of clinical efficacy and modulation of local immune responses.
Article
Engineering, Biomedical
Tom C. L. Bracco Gartner, Ye Wang, Laurynas Leiteris, Iris van Adrichem, Judith Marsman, Marie Jose Goumans, Carlijn V. C. Bouten, Joost P. G. Sluijter, Jaap M. J. den Toonder, Willem J. L. Suyker, Jesper Hjortnaes
Summary: Cardiac fibroblasts in the ever-beating human heart remain quiescent due to the antifibrotic effect of cyclic strain conditions revealed by a novel platform for studying cardiac fibrosis-on-a-chip. This study provides insights into the mechanosensitive pathways and genes involved in the fibrogenic process, which can contribute to the development of new therapies against cardiac fibrosis.
JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
(2023)
Meeting Abstract
Gastroenterology & Hepatology
Hao Dang, Tom J. Harrijvan, Anita Liao, Erik H. Danen, Noel F. de Miranda, James Hardwick, Jurjen Boonstra, Lukas Hawinkels
Meeting Abstract
Gastroenterology & Hepatology
Z. Zhou, L. G. Plug, E. S. M. de Jonge-Muller, L. M. van de Beek, L. Brands, A. E. van der Meulen-de Jong, L. J. A. C. Hawinkels, M. C. Barnhoorn
JOURNAL OF CROHNS & COLITIS
(2022)
Meeting Abstract
Gastroenterology & Hepatology
Z. Zhou, L. G. Plug, E. S. M. de Jonge-Muller, A. Abou Elmagd, A. E. van der Meulen-de Jong, M. C. Barnhoorn, L. J. A. C. Hawinkels
JOURNAL OF CROHNS & COLITIS
(2022)
Meeting Abstract
Gastroenterology & Hepatology
R. Loveikyte, A. R. Bourgonje, J. J. van der Reijden, M. L. C. Bulthuis, L. J. A. C. Hawinkels, H. van Goor, A. E. van der Meulen-de Jong, G. Dijkstra
JOURNAL OF CROHNS & COLITIS
(2022)
