The Extracellular Matrix in Soft Tissue Sarcomas: Pathobiology and Cellular Signalling

Abstract

Soft tissue sarcomas are rare cancers of mesenchymal origin or differentiation comprising over 70 different histological subtypes. Due to their mesenchymal differentiation, sarcomas are thought to produce and deposit large quantities of extracellular matrix (ECM) components. Interactions between ECM ligands and their corresponding adhesion receptors such as the integrins and the discoidin domain receptors play key roles in driving many fundamental oncogenic processes including uncontrolled proliferation, cellular invasion and altered metabolism. In this review, we focus on emerging studies that describe the key ECM components commonly found in soft tissue sarcomas and discuss preclinical and clinical evidence outlining the important role that these proteins and their cognate adhesion receptors play in sarcomagenesis. We conclude by providing a perspective on the need for more comprehensive in-depth analyses of both the ECM and adhesion receptor biology in multiple histological subtypes in order to identify new drug targets and prognostic biomarkers for this group of rare diseases of unmet need.

Clinical Prognostic Factors and Integrated Multi-Omics Studies Identify Potential Novel Therapeutic Targets for Pediatric Desmoid Tumor

“…The extracellular matrix has also been shown to be important in soft tissue sarcomas. Interactions between ECM ligands and their corresponding adhesion receptors are critical in driving many oncogenic processes like proliferation, invasion, altered metabolism and tumor immune microenvironment [15,16]. These pathways and key genes/metabolites may be important for developing potential treatment of PDTs.…”

Oncogene-induced matrix reorganization controls CD8+ T cell function in the soft-tissue sarcoma microenvironment

“…4 Includes 2 alveolar soft part sarcomas, 1 epithelioid hemangioendothelioma, 1 fibroma, 1 glomus tumor, 1 hemangioendothelial sarcoma, 1 hemangiopericytoma, 1 osteosarcoma, and 1 tenosynovial giant cell tumor. 5…”

“…Soft tissue sarcomas (STS) are heterogeneous solid mesenchymal tumors with ~70 distinct histologic subtypes (3). These lesions are characterized by mesenchymal gene expression, extensive extracellular matrix (ECM) deposition, and increased stiffness relative to normal tissues (4)(5)(6). Interestingly, these features are also observed in high-grade, poorly differentiated epithelial tumors where they are linked to progression, therapeutic resistance, and poor clinical outcomes (7).…”

Oncogene-induced matrix reorganization controls CD8+T cell function in the soft-tissue sarcoma microenvironment

“…Soft tissue sarcoma (STS) is a heterogeneous group of solid mesenchymal malignancies comprised of ~70 distinct histologic tumor subtypes [4][5][6] . Consistent with their mesenchymal origins, STS are characterized by mesenchymal gene expression, extensive secretion of extracellular matrix (ECM) components, and increased ECM stiffness relative to normal tissues [7][8][9][10] . Interestingly, these features are also observed in high-grade, poorly differentiated epithelial tumors where they are linked to progression, therapeutic resistance, and poor clinical outcomes 7,[11][12][13][14][15][16][17][18][19][20][21][22] .…”