Extracellular matrix stiffness protects carcinoma cells from sorafenib via JNK signaling

Nguyen, Thuy; Sleiman, Marianne; Moriarty, Timothy; Herrick, William G.; Peyton, Shelly R.

doi:10.1109/nebec.2014.6972891

Cited by 4 publications

(4 citation statements)

References 3 publications

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“…Similar observations have been noted for solid stress, Fernández-Sánchez et al ( 2015 ) examined that solid stress via the mechanical activation of β-cat pathway provided mechanical cues in the in vivo malignant phenotype of murine colon tissue, for inducing the transformation of surrounding normal epithelial cells into cancer cells. Nguyen et al ( 2014 ) demonstrated that the stiffness due to dense network of collagen-rich fibers also hampered the anticancer activity and conferred resistance against Raf kinase inhibitor, sorafenib.…”

Section: Understanding the Challenges And Opportunities Presented By mentioning

confidence: 99%

Tumor Microenvironment Targeted Nanotherapy

2018

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Recent developments in nanotechnology have brought new approaches to cancer diagnosis and therapy. While enhanced permeability and retention effect promotes nano-chemotherapeutics extravasation, the abnormal tumor vasculature, high interstitial pressure and dense stroma structure limit homogeneous intratumoral distribution of nano-chemotherapeutics and compromise their imaging and therapeutic effect. Moreover, heterogeneous distribution of nano-chemotherapeutics in non-tumor-stroma cells damages the non-tumor cells, and interferes with tumor-stroma crosstalk. This can lead not only to inhibition of tumor progression, but can also paradoxically induce acquired resistance and facilitate tumor cell proliferation and metastasis. Overall, the tumor microenvironment plays a vital role in regulating nano-chemotherapeutics distribution and their biological effects. In this review, the barriers in tumor microenvironment, its consequential effects on nano-chemotherapeutics, considerations to improve nano-chemotherapeutics delivery and combinatory strategies to overcome acquired resistance induced by tumor microenvironment have been summarized. The various strategies viz., nanotechnology based approach as well as ligand-mediated, redox-responsive, and enzyme-mediated based combinatorial nanoapproaches have been discussed in this review.

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Section: Understanding the Challenges And Opportunities Presented By mentioning

confidence: 99%

Tumor Microenvironment Targeted Nanotherapy

2018

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“…The situation leads to cellular transformation and metastasis, essential for tumor angiogenesis and HCC development. The efficacy of sorafenib has been reported to reduce on stiff, collagen-rich microenvironments which impairs the delivery of chemotherapeutics and promotes aggressive neoplastic cell behavior [84,89].…”

Section: Fibrosismentioning

confidence: 99%

Potential molecular, cellular and microenvironmental mechanism of sorafenib resistance in hepatocellular carcinoma

et al. 2015

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“…In the great majority of cases, a cancerous mass is a complex of tissues: an extracellular matrix (ECM), stroma, and the cancer cells derived from epithelium. In a clinical cancer, ECM is rigid whereas the tumor tissue is softer than the tissue of origin (1). The stiffness of a cell/tissue is determined by its "Young's modulus" (E) which is obtained by measuring resistance to deformity of the cell/tissue in response to a force applied for a given surface area.…”

Section: Introductionmentioning

confidence: 99%

“…Magnetic energy is transformed into mechanical energy by the magnetized particles acting as "bioactuators", applying a constraint field, and by consequence biomechanical stress to the tumor. 1 A patent application has been filed (PCT EP 2014 064995, Cell Constraint & Cancer Inc., France) to protect the applications of these findings. Generation of a field of constraint on a 2D cell culture: each particle subjected to a magnetic field gradient generates a force vector.…”

Section: Introductionmentioning

confidence: 99%

Mechanical signals inhibit growth of a grafted tumorin vivo: Proof of Concept

Brossel¹,

Yahi

David

et al. 2016

Preprint

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In the past ten years, many studies have shown that malignant tissue has been "normalized" in vitro using mechanical signals. We apply the principles of physical oncology (or mechanobiology) in vivo to show the effect of a "constraint field" on tumor growth. The human breast cancer cell line, MDA MB 231, admixed with ferric nanoparticles was grafted subcutaneously in Nude mice. The magnetizable particles rapidly surrounded the growing tumor.Two permanent magnets located on either side of the tumor created a gradient of magnetic field.Magnetic energy is transformed into mechanical energy by the particles acting as "bioactuators", applying a constraint field and, by consequence, biomechanical stress to the tumor. This On ex vivo examination, the surface of the tumor mass, measured on histologic sections, was less in the treated group, G1, than in the control groups: G2 (nanoparticles, no magnetic field), G3(magnetic field, no nanoparticles), G4 (no nanoparticles, no magnetic field) in the D 59 population (Median left surface was significantly lower in G1 (5.6 [3.0; 42.4 G3 (18.0 [14.6; 35.2]) and G4 (12.5 [1.5; 51.8]). There was no statistically significant difference in the day 59+ population. This is the first demonstration of the effect of stress on tumor growth in vivo suggesting that biomechanical intervention may have a high translational potential as a therapy in locally advanced tumors like pancreatic cancer or primary hepatic carcinoma for which no effective therapy is currently available.

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Extracellular matrix stiffness protects carcinoma cells from sorafenib via JNK signaling

Cited by 4 publications

References 3 publications

Tumor Microenvironment Targeted Nanotherapy

Tumor Microenvironment Targeted Nanotherapy

Potential molecular, cellular and microenvironmental mechanism of sorafenib resistance in hepatocellular carcinoma

Mechanical signals inhibit growth of a grafted tumorin vivo: Proof of Concept

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