Imaging aspects of the tumor stroma with therapeutic implications

Abstract

Cancer cells rely on extensive support from the stroma in order to survive, proliferate and invade. The tumor stroma is thus an important potential target for anti-cancer therapy. Typical changes in the stroma include a shift from the quiescence promoting- antiangiogenic extracellular matrix to a provisional matrix that promotes invasion and angiogenesis. These changes in the extracellular matrix are induced by changes in the secretion of extracellular matrix proteins and glucose amino glycans, extravasation of plasma proteins from hyperpermeable vessels and release of matrix modifying enzymes resulting in cleavage and crosslinking of matrix macromolecules. These in turn alter the rigidity of the matrix and the exposure and release of cytokines. Changes in matrix rigidity and vessel permeability affect drug delivery and mediate resistance to cytotoxic therapy. These stroma changes are brought about not only by the cancer cells, but also through the action of many cell types that are recruited by tumors including immune cells, fibroblasts and endothelial cells. Within the tumor, these normal host cells are activated resulting in loss of inhibitory and induction of cancer promoting activities. Key to the development of stroma targeted therapies, selective biomarkers were developed for specific imaging of key aspects of the tumor stroma.

Mesenchymal Stromal Cells Can Regulate the Immune Response in the Tumor Microenvironment

“…In this context, it is conceivable that surface markers expressed mainly, if not exclusively, by MSC should be considered to regulate the TME. Indeed, FAP, CD73, and CD105 can be considered as suitable markers to target MSC [11,13,14,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150]. In hematological malignancies, but also in solid tumors, the administration of immunomodulatory drugs (IMiDs) derived from their prototype Thalidomide to CC-122 has given very attractive results because these compounds can hit MSC besides tumor cells [151,152,153].…”

Key participants of the tumor microenvironment of the prostate: An approach of the structural dynamic of cellular elements and extracellular matrix components during epithelial–stromal transition

“…Various studies have suggested the cleavage of type I collagen as an integral component of neoplastic stroma in the structural as well as the signaling role, since proteolysis leads to the formation of biologically active collagen I peptides, which favor the proliferation and angiogenesis, while also representing a therapeutic target (Tlsty and Coussens, 2005;Ricard-Blum, 2011;Narunsky et al, 2014). These collagen I peptides, called matricryptins, increase the functional diversity of collagens because most of them possess biological activities that are different from their parent molecule (Ricard-Blum, 2011;Ricard-Blum and Ballut, 2011).…”

Fully human VEGFR2 monoclonal antibody BC001 attenuates tumor angiogenesis and inhibits tumor growth

“…Furthermore, angiogenesis of human tumor xenografts in nude mice not only depends on human tumor cells or tumor stem cells, but also requires regulation of immune cells, bone marrow-derived progenitor cells, and support from the host (38). For example, macrophages and fibroblasts, produce a wide variety of proangiogenic factors, participating in the formation of tumor blood vessels (39,40). Therefore, it was not surprising to observe that bevacizumab showed better inhibitory effect than BC001 on human tumor xenograft mouse model.…”