Extracellular matrix macromolecules: potential tools and targets in cancer gene therapy

Abstract

Tumour cells create their own microenvironment where they closely interact with a variety of soluble and non-soluble molecules, different cells and numerous other components within the extracellular matrix (ECM). Interaction between tumour cells and the ECM is bidirectional leading to either progression or inhibition of tumourigenesis. Therefore, development of novel therapies targeted primarily to tumour microenvironment (TME) is highly rational. Here, we give a short overview of different macromolecules of the ECM and introduce mechanisms whereby they contribute to tumourigenesis within the TME. Furthermore, we present examples of individual ECM macromolecules as regulators of cell behaviour during tumourigenesis. Finally, we focus on novel strategies of using ECM macromolecules as tools or targets in cancer gene therapy in the future.

Keywords: Cancer; Extracellular matrix; Gene therapy; Macromolecules; Tumour microenvironment.

Figure 1

Schematic representation of the desired effects of ECM-based gene therapies in cancer. 1. Degradation or reorganization of ECM macromolecules in the TME enables more efficient drug delivery to the tumour. 2. Degradation of ECM macromolecules, e.g. degradation of HA formed halos around cancer cells can enhance action of immune cells. 3. Encapsulation of the tumour mass with specific ECM macromolecules could inhibit tumour growth and metastasis. 4. Diminished tumour angiogenesis and lympangiogenesis can cause tumour necrosis and prevent metastasis. 5. Manipulation of 3D structure of the ECM in TME can decrease cancer cell tumourigenesis via various mechanisms. TME: tumour microenvironment.