Mechanobiology of Colorectal Cancer

Brás, M. Manuela; Sousa, Susana R.; Carneiro, Fátima; Radmacher, Manfred; Granja, Pedro L.

doi:10.3390/cancers14081945

Cited by 10 publications

(8 citation statements)

References 199 publications

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“…Altogether, our findings shed light on the regulation of cell fate transitions underlying CRC metastasis and provide novel insights into the role of mechanosensitive calcium channels in tumor malignancy. Future studies may delineate whether other pro-metastatic processes influenced by calcium influx contribute to the mechanical regulation of CRC progression (Monteith et al, 2017), and how integrins and mechanosensitive channels interact with other force-sensitive mechanisms that may impact intestinal tumors (Brás et al, 2022; Broders-Bondon et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Mechanical regulation of cell fate transitions underlying colorectal cancer metastasis formation

van der Net,

Vliem,

Kemp

et al. 2023

Preprint

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Colorectal cancer (CRC) cells exhibit high plasticity and transition between different cellular states during the development of metastasis. Lgr5-expressing cancer stem cells fuel the growth of the primary tumor and metastasis, yet disseminated tumor cells arriving at the metastatic site are devoid of Lgr5 expression. It is currently unknown how CRC cell fate transitions are regulated during the metastatic process and how tumor cells give rise to metastatic lesions despite being Lgr5neg. Here, we show that the reprogramming of disseminating CRC cells is driven by mechanical interactions with the Collagen I-rich interstitial matrix. Collagen I-induced pulling forces are sensed by integrins and mechanosensitive calcium channels, which together direct the transition of CRC cells into a fetal-like state. The fetal-like state is maintained after reaching the blood circulation and promotes metastasis-initiation of disseminated CRC cells in the liver. Our findings indicate a key contribution of mechanical signals in controlling cell fate transitions that underlie the metastatic potential of CRC, involving an interplay between different mechanosensitive mechanisms.

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Section: Discussionmentioning

confidence: 99%

Mechanical regulation of cell fate transitions underlying colorectal cancer metastasis formation

van der Net,

Vliem,

Kemp

et al. 2023

Preprint

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“…The BM is primarily composed of laminin and collagen IV and serves as a structural barrier to cancer cell invasion, intravasation, and extravasation. Cancer invasion through the BM is the initial stage of tumor dissemination and metastasis [24][25][26]. In epithelial cancers, cells must penetrate the BM to metastasize.…”

Section: Basement Membrane and Extracellular Matrixmentioning

confidence: 99%

“…Recent studies indicate protease-independent BM invasion through physical forces generated by cancer cells, involving collective cellular interactions, proliferation, CAFs, and myoepithelial and immune cells. In this hypothesis, disruption of the BM, like metastasis, involves the cells pushing through the basement membrane into the stoma [26,31]. The ability of tumor cells to form various types of actin-rich protrusions, including invasive protrusions (invadopodia) and locomotor protrusions (lamellipodia [2D] or pseudopodia [3D]), may play an important role in BM disruption and tumor cell dissemination [26,32] (see below).…”

Section: Tumor Microenvironment (Tme)mentioning

confidence: 99%

The Untouched Reserve of Cancer Chemotherapy: Tumor Cell Communication as a Promising Supramolecular Target

Alekseenko,

Zhukova,

Kondratyeva

et al. 2024

Preprint

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52 years have passed since President Nixon launched the "War on Cancer". The goals outlined by the President were not achieved because cancer treatment applied such as chemotherapy, radiotherapy, and targeted therapy have not fully met expectations. We suggest a new chemotherapeutic strategy: disrupting the communication between cancer cells and their microenvironment by chemical means. Immunological synapses that form between cancer cells and immune or other stromal cells provide an attractive target for this approach. Synapses form ligand-receptor clusters within interface of the interacting cells. Despite their differences, synapses share common properties: intercellular protein clusters; the proximity of these proteins; and their cooperative interaction making a synapse an unified functional unit. Synapses provide the limited space for the focused intercellular exchange of signaling molecules and particles. Therefore, destruction of synapses is expected to cause collapse of various tumor types. Additionally, the clustered arrangement of synapse components offers opportunities to increase treatment safety by reducing the concentration of cell impermeable agents used, to enhance its specificity applying cross-linking reagents, thus restricting modifications of surface-exposed molecules. By attaching a cleavable cell permeable toxic agent to a crosslinker should further enhance a killing potential in treating cancer. The proposed approach promises to be simple, universal, and less expensive than existing cancer therapy methods.

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“…Their results have shown that living cells tend to possess different mechanobiological properties, including viscosity and stiffness, when affected by diseases like cancer, and variations in these properties have been proposed as biomarkers for early-stage detection. 10 , 103 …”

Section: Existing Diagnostic Techniquesmentioning

confidence: 99%

Fundamentals of Bowel Cancer for Biomedical Engineers

et al. 2023

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Bowel cancer is a multifactorial disease arising from a combination of genetic predisposition and environmental factors. Detection of bowel cancer and its precursor lesions is predominantly performed by either visual inspection of the colonic mucosa during endoscopy or cross-sectional imaging. Most cases are diagnosed when the cancer is already at an advanced stage. These modalities are less reliable for detecting lesions at the earliest stages, when they are typically small or flat. Removal of lesions at the earliest possible stage reduces the risk of cancer death, which is largely due to a reduced risk of subsequent metastasis. In this review, we summarised the origin of bowel cancer and the mechanism of its metastasis. In particular, we reviewed a broad spectrum of literatures covering the biomechanics of bowel cancer and its measurement techniques that are pertinent to the successful development of a bowel cancer diagnostic device. We also reviewed existing bowel cancer diagnostic techniques that are available for clinical use. Finally, we outlined current clinical needs and highlighted the potential roles of medical robotics on early bowel cancer diagnosis.

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Mechanobiology of Colorectal Cancer

Cited by 10 publications

References 199 publications

Mechanical regulation of cell fate transitions underlying colorectal cancer metastasis formation

Mechanical regulation of cell fate transitions underlying colorectal cancer metastasis formation

The Untouched Reserve of Cancer Chemotherapy: Tumor Cell Communication as a Promising Supramolecular Target

Fundamentals of Bowel Cancer for Biomedical Engineers

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