Effect of photodynamic therapy on the extracellular matrix and associated components

Abstract

In many countries, photodynamic therapy (PDT) has been recognized as a standard treatment for malignant conditions (for example, esophageal and lung cancers) and non-malignant ones such as age-related macular degeneration and actinic keratoses. The administration of a non-toxic photosensitizer, its selective retention in highly proliferating cells and the later activation of this molecule by light to form reactive oxygen species that cause cell death is the principle of PDT. Three important mechanisms are responsible for the PDT effectiveness: a) direct tumor cell kill; b) damage of the tumor vasculature; c) post-treatment immunological response associated with the leukocyte stimulation and release of many inflammatory mediators like cytokines, growth factors, components of the complement system, acute phase proteins, and other immunoregulators. Due to the potential applications of this therapy, many studies have been reported regarding the effect of the treatment on cell survival/death, cell proliferation, matrix assembly, proteases and inhibitors, among others. Studies have demonstrated that PDT alters the extracellular matrix profoundly. For example, PDT induces collagen matrix changes, including cross-linking. The extracellular matrix is vital for tissue organization in multicellular organisms. In cooperation with growth factors and cytokines, it provides cells with key signals in a variety of physiological and pathological processes, for example, adhesion/migration and cell proliferation/differentiation/death. Thus, the focus of the present paper is related to the effects of PDT observed on the extracellular matrix and on the molecules associated with it, such as, adhesion molecules, matrix metalloproteinases, growth factors, and immunological mediators.

Photodynamic therapy with a novel porphyrin-based photosensitizer against human gastric cancer

“…Since ROS have a short half-life and are only able to act close to the site of generation (26), photodynamic damage is closely associated with the generation of ROS within cells, and therefore to the precise intracellular localization of PS. PSs are able to localize various organelles within cells, including the mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membranes (27). Generally, PS distribution in mitochondria commonly activates cell apoptosis through various pathways, while PS distribution in lysosomes frequently leads to cell necrosis (28).…”

Effects of electrophotodynamic therapy in vitro on human melanoma cells – melanotic (MeWo) and amelanotic (C32)

“…turn triggers apoptosis [40]. Photofrin localized in the endoplasmic reticulum induced changes manifested by an increase in Ca 2 + in the cytoplasm, and activation of calpains and caspase 12 [13,24].…”

Tumor Microenvironment as a Determinant of Photodynamic Therapy Resistance

“…Collagens are most abundant among the proteins of ECM, a secreted scaffold that also includes other adhesive proteins, such as fibronectin and lamin, and functions to support the assembly of cells and regulate their communication [42]. An affinity of photosensitizer for collagen is suggestive of the possibility that extracellular matrix composition may affect the PDT response.…”