Modulation of the Tumor Microenvironment for Cancer Treatment: A Biomaterials Approach

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Tumors are complex tissues that consist of stromal cells, such as fibroblasts, immune cells and mesenchymal stem cells, as well as non-cellular components, in addition to neoplastic cells. Increasingly, there is evidence to suggest that these non-neoplastic cell components support cancer initiation, progression and metastasis and that their ablation or reprogramming can inhibit tumor growth. Our understanding of the activities of different parts of the tumor stroma in advancing cancer has been improved by the use of scaffold and matrix-based 3D systems originally developed for regenerative medicine. Additionally, drug delivery systems made from synthetic and natural biomaterials deliver drugs to kill stromal cells or reprogram the microenvironment for tumor inhibition. In this article, we review the impact of 3D tumor models in increasing our understanding of tumorigenesis. We also discuss how different drug delivery systems aid in the reprogramming of tumor stroma for cancer treatment.

Related collections

Most cited references 103

Record: found
Abstract: found
Article: not found

Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting.

Chrisostomi Gialeli, Achilleas Theocharis, Nikos K Karamanos (2011)

Matrix metalloproteinases (MMPs) consist of a multigene family of zinc-dependent extracellular matrix (ECM) remodeling endopeptidases implicated in pathological processes, such as carcinogenesis. In this regard, their activity plays a pivotal role in tumor growth and the multistep processes of invasion and metastasis, including proteolytic degradation of ECM, alteration of the cell-cell and cell-ECM interactions, migration and angiogenesis. The underlying premise of the current minireview is that MMPs are able to proteolytically process substrates in the extracellular milieu and, in so doing, promote tumor progression. However, certain members of the MMP family exert contradicting roles at different stages during cancer progression, depending among other factors on the tumor stage, tumor site, enzyme localization and substrate profile. MMPs are therefore amenable to therapeutic intervention by synthetic and natural inhibitors, providing perspectives for future studies. Multiple therapeutic agents, called matrix metalloproteinase inhibitors (MMPIs) have been developed to target MMPs, attempting to control their enzymatic activity. Even though clinical trials with these compounds do not show the expected results in most cases, the field of MMPIs is ongoing. This minireview critically evaluates the role of MMPs in relation to cancer progression, and highlights the challenges, as well as future prospects, for the design, development and efficacy of MMPIs. © 2010 The Authors Journal compilation © 2010 FEBS.

0 comments Cited 497 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Distinct fibroblast lineages determine dermal architecture in skin development and repair

Ryan R. Driskell, Beate M Lichtenberger, Esther Hoste … (2013)

Fibroblasts are the major mesenchymal cell type in connective tissue and deposit the collagen and elastic fibers of the extracellular matrix (ECM) 1 . Even within a single tissue fibroblasts exhibit remarkable functional diversity, but it is not known whether this reflects the existence of a differentiation hierarchy or is a response to different environmental factors. Here we show, using transplantation assays and lineage tracing, that the fibroblasts of skin connective tissue arise from two distinct lineages. One forms the upper dermis, including the dermal papilla that regulates hair growth and the arrector pili muscle (APM), which controls piloerection. The other forms the lower dermis, including the reticular fibroblasts that synthesise the bulk of the fibrillar ECM, and the pre-adipocytes and adipocytes of the hypodermis. The upper lineage is required for hair follicle formation. In wounded adult skin, the initial wave of dermal repair is mediated by the lower lineage and upper dermal fibroblasts are recruited only during re-epithelialisation. Epidermal beta-catenin activation stimulates expansion of the upper dermal lineage, rendering wounds permissive for hair follicle formation. Our findings explain why wounding is linked to formation of ECM-rich scar tissue that lacks hair follicles 2-4 . They also form a platform for discovering fibroblast lineages in other tissues and for examining fibroblast changes in ageing and disease.

0 comments Cited 438 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Normalizing tumor microenvironment to treat cancer: bench to bedside to biomarkers.

Rakesh Jain (2013)

For almost four decades, my work has focused on one challenge: improving the delivery and efficacy of anticancer therapeutics. Working on the hypothesis that the abnormal tumor microenvironment-characterized by hypoxia and high interstitial fluid pressure--fuels tumor progression and treatment resistance, we developed an array of sophisticated imaging technologies and animal models as well as mathematic models to unravel the complex biology of tumors. Using these tools, we demonstrated that the blood and lymphatic vasculature, fibroblasts, immune cells, and extracellular matrix associated with tumors are abnormal, which together create a hostile tumor microenvironment. We next hypothesized that agents that induce normalization of the microenvironment can improve treatment outcome. Indeed, we demonstrated that judicious use of antiangiogenic agents--originally designed to starve tumors--could transiently normalize tumor vasculature, alleviate hypoxia, increase delivery of drugs and antitumor immune cells, and improve the outcome of various therapies. Our trials of antiangiogenics in patients with newly diagnosed and recurrent glioblastoma supported this concept. They revealed that patients whose tumor blood perfusion increased in response to cediranib survived 6 to 9 months longer than those whose blood perfusion did not increase. The normalization hypothesis also opened doors to treating various nonmalignant diseases characterized by abnormal vasculature, such as neurofibromatosis type 2. More recently, we discovered that antifibrosis drugs capable of normalizing the tumor microenvironment can improve the delivery and efficacy of nano- and molecular medicines. Our current efforts are directed at identifying predictive biomarkers and more-effective strategies to normalize the tumor microenvironment for enhancing anticancer therapies.

0 comments Cited 406 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Sue Anne Chew: Role: Academic Editor

Journal

Journal ID (nlm-ta): J Funct Biomater

Journal ID (iso-abbrev): J Funct Biomater

Journal ID (publisher-id): jfb

Title: Journal of Functional Biomaterials

Publisher: MDPI

ISSN (Electronic): 2079-4983

Publication date (Electronic): 17 February 2015

Publication date Collection: March 2015

Volume: 6

Issue: 1

Pages: 81-103

Affiliations

Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611, USA; E-Mail: adjeii@ 123456ufl.edu

Author notes

[* ]Author to whom correspondence should be addressed; E-Mail: blanka.sharma@ 123456bme.ufl.edu ; Tel.: +1-352-273-9329; Fax: +1-352-273-2991.

Article

Publisher ID: jfb-06-00081

DOI: 10.3390/jfb6010081

PMC ID: 4384103

PubMed ID: 25695337

SO-VID: 3d92afca-72ad-48a5-8d15-da110ad2377b

License:

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

Modulation of the Tumor Microenvironment for Cancer Treatment: A Biomaterials Approach

Read this article at

Abstract

Related collections

Karger: Ophthalmology

Most cited references 103

Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting.

Distinct fibroblast lineages determine dermal architecture in skin development and repair

Normalizing tumor microenvironment to treat cancer: bench to bedside to biomarkers.

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 373

Cited by 30

Most referenced authors 2,230