Fibrosis, Cancer and the Premetastatic Niche

Cox, Thomas R.; Erler, Janine T.

doi:10.2217/bmt.14.36

Cited by 5 publications

(7 citation statements)

References 22 publications

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“…Therefore, the following questions have arisen: why is the colonization of tumor cells (including the H1299 cell line) correlated with tissues with high ECM density, such as bone 47 , which has an ECM more than 10 5 times more rigid than that found in other matrices in soft tissues 36 , 48 ? What explains the link, which has been reported both in vivo and in vitro , between desmoplasia (the growth of fibrous or connective tissue) and a higher probability of colonization by tumor cells 49 – 51 ?…”

Section: Discussionmentioning

confidence: 97%

From individual to collective 3D cancer dissemination: roles of collagen concentration and TGF-β

Plou

Juste-Lanas

Olivares

et al. 2018

Sci Rep

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Cancer cells have the ability to migrate from the primary (original) site to other places in the body. The extracellular matrix affects cancer cell migratory capacity and has been correlated with tissue-specific spreading patterns. However, how the matrix orchestrates these behaviors remains unclear. Here, we investigated how both higher collagen concentrations and TGF-β regulate the formation of H1299 cell (a non-small cell lung cancer cell line) spheroids within 3D collagen-based matrices and promote cancer cell invasive capacity. We show that at low collagen concentrations, tumor cells move individually and have moderate invasive capacity, whereas when the collagen concentration is increased, the formation of cell clusters is promoted. In addition, when the concentration of TGF-β in the microenvironment is lower, most of the clusters are aggregates of cancer cells with a spheroid-like morphology and poor migratory capacity. In contrast, higher concentrations of TGF-β induced the formation of clusters with a notably higher invasive capacity, resulting in clear strand-like collective cell migration. Our results show that the concentration of the extracellular matrix is a key regulator of the formation of tumor clusters that affects their development and growth. In addition, chemical factors create a microenvironment that promotes the transformation of idle tumor clusters into very active, invasive tumor structures. These results collectively demonstrate the relevant regulatory role of the mechano-chemical microenvironment in leading the preferential metastasis of tumor cells to specific tissues with high collagen concentrations and TFG-β activity.

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Section: Discussionmentioning

confidence: 97%

From individual to collective 3D cancer dissemination: roles of collagen concentration and TGF-β

Plou

Juste-Lanas

Olivares

et al. 2018

Sci Rep

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“…The hydrogel matrix used in our work recapitulated the structural and biochemical properties of the fibrillar breast tumor ECM. [54][55][56][57] Furthermore, owing to its chemical crosslinking, the EKGel tolerated the shear stress imposed by the flow of the cell culture medium and drug solution. We showed the utility of the MF platform for time-efficient (within 6 days) studies of the flow-and dose-dependent response of breast cancer spheroids to anticancer drugs.…”

Section: Discussionmentioning

confidence: 99%

“…The hydrogel's fibrillar architecture recapitulated the fibrotic nature of the breast tumor ECM, which is composed of a dense network of collagen filaments. [54][55][56][57] The hydrogel, referred to as "EKGel" below, was chemically crosslinked via the reaction of aldehyde-modified cellulose nanocrystals (a-CNCs) and the primary amine groups of the lysine residues in gelatin (Figure S2, Supporting Information). Chemical crosslinking ensured hydrogel integrity under continuous flow of the cell culture medium.…”

Section: Microfluidic Arrays Of Mfc-7 Breast Tumor Spheroidsmentioning

confidence: 99%

Microfluidic Arrays of Breast Tumor Spheroids for Drug Screening and Personalized Cancer Therapies

Prince

Kheiri

Wang

et al. 2021

Adv Healthcare Materials

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One of the obstacles limiting progress in the development of effective cancer therapies is the shortage of preclinical models that capture the dynamic nature of tumor microenvironments. Interstitial flow strongly impacts tumor response to chemotherapy; however, conventional in vitro cancer models largely disregard this key feature. Here, a proof of principle microfluidic platform for the generation of large arrays of breast tumor spheroids that are grown under close-to-physiological flow in a biomimetic hydrogel is reported. This cancer spheroids-on-a-chip model is used for time-and labor-efficient studies of the effects of drug dose and supply rate on the chemosensitivity of breast tumor spheroids. The capability to grow large arrays of tumor spheroids from patient-derived cells of different breast cancer subtypes is shown, and the correlation between in vivo drug efficacy and on-chip spheroid drug response is demonstrated. The proposed platform can serve as an in vitro preclinical model for the development of personalized cancer therapies and effective screening of new anticancer drugs.

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“…The capability of using EKGel as a scaffold for in vitro studies of fibrosis was then validated by demonstrating that it is a compatible matrix for the culture of multiple cell types relevant to fibrotic disease, including breast cancer cells and human dermal fibroblasts (HDFs). Fibrosis occurs in breast cancer and in other solid tumors, − and the alteration of ECM properties during tumor progression is associated with aggressive and metastatic phenotypes. ,, We show the suitability of EKGel for in vitro studies of fibrosis in breast tumors by growing tumor spheroids from MCF-7 and MDA-MB-231 cells and examining how hydrogel structure and properties impact spheroid growth.…”

Section: Introductionmentioning

confidence: 92%

Nanofibrillar Hydrogel Recapitulates Changes Occurring in the Fibrotic Extracellular Matrix

et al. 2021

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Fibrosis is a pathological condition that leads to excessive deposition of collagen and increased tissue stiffness. Understanding the mechanobiology of fibrotic tissue necessitates the development of effective in vitro models that recapitulate its properties and structure; however, hydrogels that are currently used for this purpose fail to mimic the filamentous structure and mechanical properties of the fibrotic extracellular matrix (ECM). Here, we report a nanofibrillar hydrogel composed of cellulose nanocrystals and gelatin, which addresses this challenge. By altering the composition of the hydrogel, we mimicked the changes in structure, mechanical properties, and chemistry of fibrotic ECM. Furthermore, we decoupled the variations in hydrogel structure, properties, and ligand concentration. We demonstrate that this biocompatible hydrogel supports the three-dimensional culture of cells relevant to fibrotic diseases. This versatile hydrogel can be used for in vitro studies of fibrosis of different tissues, thus enabling the development of novel treatments for fibrotic diseases.

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Fibrosis, Cancer and the Premetastatic Niche

Cited by 5 publications

References 22 publications

From individual to collective 3D cancer dissemination: roles of collagen concentration and TGF-β

From individual to collective 3D cancer dissemination: roles of collagen concentration and TGF-β

Microfluidic Arrays of Breast Tumor Spheroids for Drug Screening and Personalized Cancer Therapies

Nanofibrillar Hydrogel Recapitulates Changes Occurring in the Fibrotic Extracellular Matrix

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