Biological role of matrix stiffness in tumor growth and treatment

Abstract

In recent years, the biological role of changes in physical factors in carcinogenesis and progression has attracted increasing attention. Matrix stiffness, also known as ECM stress, is a critical physical factor of tumor microenvironment and remains alternating during carcinogenesis as a result of ECM remodeling through activation of cancer-associated fibroblasts and extracellular collagen accumulation, crosslinking and fibrosis. Different content and density of extracellular collagen in ECM endows matrix with varying stiffness. Physical signals induced by matrix stiffness are transmitted to tumor cells primarily by the integrins receptor family and trigger a series of mechanotransduction that result in changes in tumor cell morphology, proliferative capacity, and invasive ability. Importantly, accumulating evidence revealed that changes in matrix stiffness in tumor tissues greatly control the sensitivity of tumor cells in response to chemotherapy, radiotherapy, and immunotherapy through integrin signaling, YAP signaling, and related signaling pathways. Here, the present review analyzes the current research advances on matrix stiffness and tumor cell behavior with a view to contributing to tumor cell growth and treatment, with the hope of improving the understanding of the biological role of matrix stiffness in tumors.

A review of bioengineering techniques applied to breast tissue: Mechanical properties, tissue engineering and finite element analysis

“…Collagens are the most abundant structural proteins in ECM, which provide support, mediate drug resistance, promote tumor progression and aggressive cell transformation, and affect the mechanics of the tissue (Tamayo-Angorrilla et al, 2022) Therefore, different content and density of collagens have a significant impact on tissue stiffness and its variation (Deng et al, 2022), which will be sensed by cancer cells (Mierke, 2021) and, hence, influence cancer progression (Cavo et al, 2016) The morphology, proliferation capacity and invasive ability of cancer cells change as a result of the mechanotransduction process of the physical signals send by the ECM stiffness (Deng et al, 2022). Moreover, ECM stiffness also has an impact on the response to cancer treatments (Tamayo-Angorrilla et al, 2022), by controlling the sensitivity of the tumor cells (Deng et al, 2022). Acerbi et al (2015) observed the collagen accumulation in breast cancer as well as the linearization and thickening of the interstitial collagen.…”

“…During carcinogenesis, the stiffness of ECM is continuously changing due to ECM remodeling, which involves activation of cancer-associated fibroblasts and excessive extracellular collagen deposition, crosslink, and fibrosis ( Keller et al, 2021 ; Deng et al, 2022 ; Tamayo-Angorrilla et al, 2022 ). Collagens are the most abundant structural proteins in ECM, which provide support, mediate drug resistance, promote tumor progression and aggressive cell transformation, and affect the mechanics of the tissue ( Tamayo-Angorrilla et al, 2022 ) Therefore, different content and density of collagens have a significant impact on tissue stiffness and its variation ( Deng et al, 2022 ), which will be sensed by cancer cells ( Mierke, 2021 ) and, hence, influence cancer progression ( Cavo et al, 2016 ) The morphology, proliferation capacity and invasive ability of cancer cells change as a result of the mechanotransduction process of the physical signals send by the ECM stiffness ( Deng et al, 2022 ). Moreover, ECM stiffness also has an impact on the response to cancer treatments ( Tamayo-Angorrilla et al, 2022 ), by controlling the sensitivity of the tumor cells ( Deng et al, 2022 ).…”

Matrix stiffness triggers chemoresistance through elevated autophagy in pancreatic ductal adenocarcinoma

“…6 Additionally, the increased deposition and crosslinking of ECM components lead to a stiffened matrix, which contributes to tumor development and progression. [7][8][9] Substantial evidences have shown that increased matrix stiffness promotes invasion and metastasis of tumor cells, enhances immune cell infiltration, gives an impetus to stem cell differentiation and so on. [10][11][12] Intriguingly, recent findings indicate that there exists a correlation between matrix stiffness and chemotherapy resistance.…”

Challenges and Opportunities for Extracellular Vesicles in Clinical Oncology Therapy

“…Cell softness is a kind of biomechanical property; tumor tissue is usually stiffer than normal tissue due to abnormal production and the crosslinking of extracellular matrix proteins, but individual tumor cells are usually softer than non-malignant cells. Current research has proved that the reduction in tumor cell stiffness is related to the transformation, malignancy, and metastasis of cancer cells [ 47 , 48 ]. Therefore, we established a method based on the biomechanical screening and three-dimensional soft fibrin gel culture of functional cancer stem cells (defined as “tumor-repopulating cells”, TRC) [ 49 ].…”