Article
Medicine, Research & Experimental
Sanghyuk Choi, Jinyeong Yu, Wootak Kim, Ki-Sook Park
Summary: In this study, N-cadherin was identified as a key molecule in mediating the migration of BM-MSCs towards breast tumors. The expression of N-cadherin increased on the intercellular borders of BM-MSCs through TGF-beta canonical signaling, leading to their collective migration in response to breast tumor cells via N-cadherin-dependent cell-cell adhesion. This introduces a novel and promising strategy for controlling and re-engineering the breast tumor microenvironment.
Article
Biochemistry & Molecular Biology
Jinok Noh, Jinyeong Yu, Wootak Kim, Aran Park, Ki-Sook Park
Summary: The tumor microenvironment in prostate cancer plays vital roles in tumor cell metastasis and re-growth. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are crucial in forming this microenvironment. The study found that N-cadherin is a key mediator of BM-MSCs migration towards hormone-insensitive prostate tumor cells.
Review
Oncology
Maria Kalli, Matthew D. Poskus, Triantafyllos Stylianopoulos, Ioannis K. Zervantonakis
Summary: This article reviews the impact of mechanical abnormalities in the tumor microenvironment on cellular signaling and drug therapy during tumor progression. It discusses drugs that can normalize these abnormalities or block mechanosensors and mechanotransduction pathways. Challenges and prospects for developing new strategies targeting mechanically induced drug resistance in the clinic are also discussed.
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
Biochemistry & Molecular Biology
Howard E. Boudreau, Agnieszka Korzeniowska, Thomas L. Leto
Summary: In this study, the authors investigated the role of mutant p53-induced NOX4 on the cancer cell secretome and the effects NOX4 signaling have on the tumor microenvironment (TME). They found that conditioned media from cells expressing mutant p53 promoted cell migration and invasion, and these effects were diminished when NOX4 was inhibited. Additionally, they identified CCL5 as a key factor in promoting cell migration, and demonstrated its crosstalk with TGF-beta from M2-polarized macrophages. These findings provide further insight into NOX4-based communication in the TME and its potential as a therapeutic target.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Materials Science, Biomaterials
Yuanyuan Liu, Jiguo Xie, Xiaofei Zhao, Yueyue Zhang, Zhiyuan Zhong, Chao Deng
Summary: A novel polymeric IDO inhibitor was developed for cancer immunotherapy, demonstrating significant tumor suppression and prolonged survival through efficient co-delivery of chemotherapeutics and inhibitors.
BIOMATERIALS SCIENCE
(2022)
Article
Oncology
Bangling Han, Tianyi Fang, Yao Zhang, Yongle Zhang, Jialiang Gao, Yingwei Xue
Summary: TGF beta is a cytokine involved in regulating cellular processes in the tumor microenvironment. It is highly expressed in many cancers and is associated with the expression of genes related to epithelial mesenchymal transition. TGF beta inhibits the antitumor function of immune cells and limits the efficacy of immunotherapeutic approaches. This study comprehensively analyzed the role of TGF beta in gastric cancer and identified its potential mechanisms.
FRONTIERS IN ONCOLOGY
(2022)
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)
Article
Chemistry, Medicinal
Norlaily Mohd Ali, Swee Keong Yeap, Wan Yong Ho, Lily Boo, Huynh Ky, Dilan Amila Satharasinghe, Sheau Wei Tan, Soon Keng Cheong, Hsien Da Huang, Kuan Chun Lan, Men Yee Chiew, Han Kiat Ong
Summary: Breast cancer is the most frequently diagnosed cancer in women globally, and TME and MSCs play crucial roles in inducing dormancy of breast cancer cells, with exosomal miRNAs potentially serving as important therapeutic targets.
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.
Review
Gastroenterology & Hepatology
Keisaku Sato, Wenjun Zhang, Samira Safarikia, Abdulkadir Isidan, Angela M. Chen, Ping Li, Heather Francis, Lindsey Kennedy, Leonardo Baiocchi, Domenico Alvaro, Shannon Glaser, Burcin Ekser, Gianfranco Alpini
Summary: Current study summaries the methodologies for organoid/spheroid formation and the potential for three-dimensional hepatic cell cultures as in vitro models of cholangiopathies.
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
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.
