title: 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 cross-linking 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.
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Lian
authors.initials: L
authors.lastname: Narunsky
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Roni
authors.initials: R
authors.lastname: Oren
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Filip
authors.initials: F
authors.lastname: Bochner
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: michal.neeman@weizmann.ac.il.
authors.forename: Michal
authors.initials: M
authors.lastname: Neeman
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor
keywords: 2P; Angiogenesis; BLI; CAFs; CARs; CFP; CMP; CT; CTL; Cancer associated fibroblasts; DCE-MRI; DCs; ECM; Extracellular matrix; FAP; FAPα; FMT; FN; HA; HLA; HSV-tk; Hyal; ICG; IL-13; Immune cells; Indocyanine green; LN; LP-ICG; MHC; MMPs; MRI; Matrix metallo proteinases; NIRF; OCT; OVA; PDGF; PET; SHG; SPECT; SPIO; TAM; TILs; TMR; Tumor microenvironment; VEGF; aSMA; alpha smooth muscle actin; bioluminescence imaging; cancer associated fibroblasts; chimeric antigen receptors; collagen mimetic peptides; computerized tomography; cyan fluorescent protein; cytotoxic T lymphocytes; dendritic cells; dynamic contrast-enhanced MRI; extracellular matrix; fibroblast activation protein; fibroblast activation protein-alpha; fibronectin; flat-panel volume computed tomography; fluorescence molecular tomography; fpVCT; herpes simplex virus thymidine kinase; human leukocyte antigen; hyaluronan; hyaluronidase; hydrophobic tetramethylrhodamine; interleukin 13; liposomal formulation of indocyanine green; lymph node; magnetic resonance imaging; major histocompatibility complex; matrix metallo proteinases; near infra-red fluorescence; optical coherence tomography; ovalbumin; platelet derived growth factor; positron emission tomography; second harmonic generation; single photon emission computerized tomography; superparamagnetic iron oxide; tumor associated macrophages; tumor infiltrating lymphocytes; two photon; vascular endothelial growth factor