Tumor Cell Mechanosensitivity: Molecular Basis

Editors

Xian Hu

University of Oslo

Mingxi Yao

Southern University of Science and Technology

Kay Oliver Schink

Norwegain Radium Hospital Research Foundation

Michael Sheetz

University of Texas Medical Branch at Galveston

Claudia Tanja Mierke

Leipzig University

Impact

Schematic of VWF and hematogenous cancer metastasis under flow. Cancer cells detach from a primary tumor, enter a nearby blood vessel (1. Intravasation) and circulate in the bloodstream. Some circulating tumor cells eventually adhere to EC in the blood vessel wall (2. Adhesion) and extravasate from the EC (3. Extravasation) to form a secondary tumor. VWF is a mediator to regulate the interactions between cancer cells, EC, and platelets. VWF also provides a “bridge” to recruit cancer cells directly or through platelets to the EC surface. Flow can not only elongate and activate VWF to bind platelets or other VWF molecules to form VWF strings, but also mediate cancer adhesion and migration. Flow is changed from shear flow in normal blood vessels to elongational flow in blood vessels with junctions/branches, stenosis, or bleeding. This figure was created with BioRender.com.

Mini Review

30 August 2024

Von Willebrand factor and hematogenous cancer metastasis under flow

Wenxuan Xu

, 4 more and

Hongxia Fu

1,854 views

1 citations

The functions of FHL2 as a mechanotransducer in the cell on a rigid or soft substrate (Left) FHL2 localizes at Focal adhesion or tense F-actin in the cell on rigid substrate (Right) FHL2 localizes to the nucleus on soft substrate, resulting in its binding to a specific promoter of the gene with transcriptional factor for cell proliferation.

Mini Review

26 July 2024

The roles of FHL2 as a mechanotransducer for cellular functions in the mechanical environment

Yukari Fujimoto

and

Naotaka Nakazawa

1,931 views

1 citations

Brief Research Report

17 July 2024

Differential Talin cleavage in transformed and non-transformed cells and its consequences

Xian Hu

, 4 more and

Michael Sheetz

1,436 views

1 citations

Review

17 April 2024

The hidden messengers: cancer associated fibroblasts—derived exosomal miRNAs as key regulators of cancer malignancy

Zixuan Gou

, 2 more and

Na Yang

Functions of CAF-derived exosomal miRNA in promoting tumorigenesis and cancer development. TME comprises various cell types, including stromal cells, immune cells, tumor cells, and so on. All these cells were enveloped in ECM (Fang et al., 2023). CAFs, as an important component of TME, can participate in tumor regulation by secreting exosomal miRNAs (Wang J. W. et al., 2019). These miRNAs can take part in immune modulation (Zhao et al., 2022), tumor growth (Shi L. et al., 2022), migration and invasion (Chen B. et al., 2021), EMT (Zhang Y. et al., 2022), and treatment resistance (Fang et al., 2019) (ECM: extracellular matrix; TME: tumor microenvironment; EMT: epithelial-mesenchymal transition). (By Figdraw).

Cancer-associated fibroblasts (CAFs), a class of stromal cells in the tumor microenvironment (TME), play a key role in controlling cancer cell invasion and metastasis, immune evasion, angiogenesis, and resistance to chemotherapy. CAFs mediate their activities by secreting soluble chemicals, releasing exosomes, and altering the extracellular matrix (ECM). Exosomes contain various biomolecules, such as nucleic acids, lipids, and proteins. microRNA (miRNA), a 22–26 nucleotide non-coding RNA, can regulate the cellular transcription processes. Studies have shown that miRNA-loaded exosomes secreted by CAFs engage in various regulatory communication networks with other TME constituents. This study focused on the roles of CAF-derived exosomal miRNAs in generating cancer malignant characteristics, including immune modulation, tumor growth, migration and invasion, epithelial-mesenchymal transition (EMT), and treatment resistance. This study thoroughly examines miRNA’s dual regulatory roles in promoting and suppressing cancer. Thus, changes in the CAF-derived exosomal miRNAs can be used as biomarkers for the diagnosis and prognosis of patients, and their specificity can be used to develop newer therapies. This review also discusses the pressing problems that require immediate attention, aiming to inspire researchers to explore more novel avenues in this field.

4,730 views

9 citations

Regulation of NRP1 expression in cells cultured on substrates with different stiffness. (A) Relative expression of NRP1 transcript in HPrEC, HEK293, HeLa, and PC-3 cells cultured for 24 h on PAA hydrogels of the indicated stiffness. (B) Relative expression of NRP1 transcript in HPrEC and PC-3 cells cultured for 12–72 h on PAA hydrogels of the indicated stiffness, the expression in cells cultured over 0.15 kPa at 12 h was considered as 1. (C) Percentage of NRP1 expressing HPrEC, HEK293, HeLa, and PC-3 cells cultured on the PAA hydrogels for 24 and 48 h (D) NRP1 mean fluorescent intensity (MFI) of HPrEC, HEK293, HeLa, and PC-3 cells cultured for 24 and 48 h on PAA hydrogels measured by flow cytometry. *p < 0.05, (A) Kruskal-Wallis followed by Dunn-Bonferroni’s multiple comparisons test (HPrEC, HEK293, and PC-3) and One-way ANOVA with Tukey’s multiple comparisons test (HeLa); triplicates from three independent experiments, and (B) Kruskal-Wallis followed by Dunn-Bonferroni’s multiple comparisons tests (HPrEC 12, 24, 72 h and PC-3 12, 48 h) and One-way ANOVA with Tukey’s multiple comparisons test (HPrEC 48 h and PC-3 24, 72 h); triplicates from two independent experiments. (C) One-way ANOVA with Tukey’s multiple comparisons test from three independent experiments. MFI, mean fluorescent intensity.

Original Research

05 June 2024

Differential modulation of cell morphology, migration, and Neuropilin-1 expression in cancer and non-cancer cell lines by substrate stiffness

Ana Monserrat Vela-Alcántara

, 6 more and

Elisa Tamariz

2,322 views

2 citations

Review

22 November 2022

The application of mechanobiotechnology for immuno-engineering and cancer immunotherapy

Chi Woo Yoon

, 1 more and

Yingxiao Wang

Immune-engineering is a rapidly emerging field in the past few years, as immunotherapy evolved from a paradigm-shifting therapeutic approach for cancer treatment to promising immuno-oncology models in clinical trials and commercial products. Linking the field of biomedical engineering with immunology, immuno-engineering applies engineering principles and utilizes synthetic biology tools to study and control the immune system for diseases treatments and interventions. Over the past decades, there has been a deeper understanding that mechanical forces play crucial roles in regulating immune cells at different stages from antigen recognition to actual killing, which suggests potential opportunities to design and tailor mechanobiology tools to novel immunotherapy. In this review, we first provide a brief introduction to recent technological and scientific advances in mechanobiology for immune cells. Different strategies for immuno-engineering are then discussed and evaluated. Furthermore, we describe the opportunities and challenges of applying mechanobiology and related technologies to study and engineer immune cells and ultimately modulate their function for immunotherapy. In summary, the synergetic integration of cutting-edge mechanical biology techniques into immune-engineering strategies can provide a powerful platform and allow new directions for the field of immunotherapy.

5,051 views

8 citations