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Review
. 2019 Aug 12:10:887.
doi: 10.3389/fphar.2019.00887. eCollection 2019.

Reversing the Tumor Target: Establishment of a Tumor Trap

Mathie Najberg  1   2 , Muhammad Haji Mansor  1   3 , Frank Boury  1 , Carmen Alvarez-Lorenzo  2 , Emmanuel Garcion  1
Affiliations
Review

Reversing the Tumor Target: Establishment of a Tumor Trap

Mathie Najberg et al. Front Pharmacol. .

Abstract

Despite the tremendous progress made in the field of cancer therapy in recent years, certain solid tumors still cannot be successfully treated. Alongside classical treatments in the form of chemotherapy and/or radiotherapy, targeted treatments such as immunotherapy that cause fewer side effects emerge as new options in the clinics. However, these alternative treatments may not be useful for treating all types of cancers, especially for killing infiltrative and circulating tumor cells (CTCs). Recent advances pursue the trapping of these cancer cells within a confined area to facilitate their removal for therapeutic and diagnostic purposes. A good understanding of the mechanisms behind tumor cell migration may drive the design of traps that mimic natural tumor niches and guide the movement of the cancer cells. To bring this trapping idea into reality, strong efforts are being made to create structured materials that imitate myelinated fibers, blood vessels, or pre-metastatic niches and incorporate chemical cues such as chemoattractants or adhesive proteins. In this review, the different strategies used (or could be used) to trap tumor cells are described, and relevant examples of their performance are analyzed.

Keywords: biomimetic trap; cancer therapy; premetastatic niche recruitment; tumor cell migration; tumor trap.

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Figures

Figure 1
Figure 1
Summary of the strategies that can be applied to fight cancers. (Scheme I) The classic treatments used for cancers are surgery, chemotherapy, and radiotherapy. (Scheme II) Innovative treatments include (1) locoregional therapy, (2) targeted therapy, and (3) tumor traps, among others. Tumor traps can be designed to take advantage of the migration pathways used by the tumor cells. It includes the use of tracks [(a) system developed by Jain et al. (2014) using aligned PCL fibers coated with laminin]. Tumor traps can be designed as synthetic pre-metastatic niches [(b) system developed by Seib et al. (2015) using a silk scaffold loaded with bone morphogenic protein 2 (BMP-2) capable of developing bone and marrow in vivo, (c) system developed by De Vlieghere et al. (2015) using iron oxide-coated microparticles encapsulating cancer-associative fibroblasts (CAFs) that continuously deposit ECM on the surface, (d) system developed by Azarin et al. (2015) using poly(lactide-co-glycolic acid) (PLGA) through the induction of the immune system by the CCL22 chemokine, and (e) system developed by De La Fuente et al. (2015) using a three-dimensional scaffold loaded with exosomes]. Finally, tumor traps can use chemoattractive molecules [(f) system developed by Giarra et al. (2018) using a methylcellulose (MC) thermo-responsive hydrogel loaded with stromal derived factor-1 (SDF-1) and (g) the system developed by Haji Mansor et al. (2018) using SDF-1 encapsulated in PLGA nanoparticles]. (4) Tumor traps can also be used for the early detection of metastasis [(a) system developed by Yoon et al. (2013) using graphene oxide nanosheets, (b) CELLSEARCH® CTC test (CELLSEARCH Circulating Tumor Cell, 2019) is a device using ferrofluid nanoparticles with EpCAM antibodies, and (c) system developed by Chen et al. (2016) using a nanoroughened glass substrate].
Figure 2
Figure 2
Schematic representation of theorized paths of cancer cell migration away from the primary tumor. (1) Migration away from the primary tumor. Tumor cells can follow aligned tracks (a), or gradients of chemoattractant in solution (chemotaxis) or fixed on a substrate (haptotaxis) through the ECM. If the cross-sectional area of the interfibrillar pore is more than 7 µm², degradation of the matrix is not needed (b); otherwise, a leader cell creates a path for the following cells thanks to MMPs (c). (2) Tumor cells adhere to a vessel and intravasate to reach the blood or lymphatic stream in which they circulate. (3) Once they reach a location where they can adhere to the vessel wall, the cells extravasate. (4) If the environment is favorable, a secondary tumor grows.
Figure 3
Figure 3
Mechanisms of arrest of a CTC: the influence of the shear force and the blood vessel diameter on the site of CTC extravasation.
Figure 4
Figure 4
Illustration of the use of scaffolds to attract motile tumor cells by chemotaxis (A) or haptotaxis (B).
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