Background: Soft tissue sarcomas are a group of neoplasms with differentiation towards mesenchymal tissue, many of which are aggressive and chemotherapy resistant. Histology and immunoprofiles often overlap with neoplasms of other lineages, and establishing an accurate histopathological diagnosis is crucial for correct management, and therapeutic stratification. The endosialin cell surface glycoprotein is predominantly expressed by stromal fibroblasts and pericytes in epithelial neoplasms; however, tumour cell expression has been reported in small series of sarcomas.
Methods: We assessed endosialin expression by immunohistochemistry in a large set of 514 human soft tissue sarcomas.
Results: Tumour cell endosialin expression was seen in 89% of undifferentiated pleomorphic sarcomas (104/117), 77% adult fibrosarcomas/spindle cell sarcomas (20/26), 62% synovial sarcomas (37/60), 51% leiomyosarcomas (94/185) and 31% rhabdomyosarcomas (39/126).
Conclusions: Endosialin immunohistochemistry has potential to distinguish undifferentiated and poorly differentiated sarcomas from other poorly differentiated, non-mesenchymal neoplasms. A Phase II trial randomising patients with advanced sarcomas to receive chemotherapy with/without an endosialin therapeutic antibody has recently completed enrolment. Endosialin expression could be used to select patients for such clinical trials. Based on our results, patients with undifferentiated pleomorphic sarcoma may be particularly suitable for such a therapeutic approach.
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http://dx.doi.org/10.1038/bjc.2016.214 | DOI Listing |
Lab Invest
January 2025
Unité de Recherche en Pharmaco-Immunologie (UR-EPI), Université et CHU de La Réunion, Saint-Denis, France; Service d'Anatomie et Cytologie Pathologiques, CHU de La Réunion site SUD-Saint-Pierre, Saint-Pierre Cedex, France; Tumorothèque régionale de La Réunion, CHU de La Réunion site SUD-Saint-Pierre, Saint-Pierre Cedex, France. Electronic address:
CD248 (endosialin/tumor endothelial marker 1) is upregulated in cancer, including colorectal cancer (CRC), but its exact role in tumor progression remains to be elucidated. Previous studies have shown that the extracellular domain of CD248 mediates the interaction between tumor cells and extracellular matrix proteins and that interfering with this interaction may reduce tumor invasion and migration activities. We have examined the expression of CD248 in 117 human CRC samples by immunohistochemistry and investigated the association with various clinicopathologic features, including the occurrence of metastasis, intratumoral immune cell density and overall survival.
View Article and Find Full Text PDFJ Immunother Cancer
September 2024
Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi'an, China
Background And Aims: Endosialin, also known as tumor endothelial marker1 or CD248, is a transmembrane glycoprotein that is mainly expressed in cancer-associated fibroblasts (CAFs) in hepatocellular carcinoma (HCC). Our previous study has found that endosialin-positive CAFs could recruit and induce the M2 polarization of macrophages in HCC. However, whether they may regulate other types of immune cells to promoting HCC progression is not known.
View Article and Find Full Text PDFInt J Biol Sci
August 2024
Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Tumor endothelial marker 1 (TEM1), an activated mesenchymal cell marker, is implicated in tissue remodeling and repair. Herein, we investigated the role and therapeutic implications of TEM1 in abdominal aortic aneurysm (AAA), a potentially life-threatening aortic disease characterized by vascular inflammation and matrix turnover. Characterization of human AAA revealed increased TEM1 expression derived mainly from medial vascular smooth muscle cells (VSMCs) and adventitial fibroblasts.
View Article and Find Full Text PDFAngiogenesis
May 2024
Department of Surgery, University of Colorado Anschutz Medical Campus, 12800 E 19th Avenue, RC1-North, P18-8116, Aurora, CO, 80045, USA.
C-type lectins, distinguished by a C-type lectin binding domain (CTLD), are an evolutionarily conserved superfamily of glycoproteins that are implicated in a broad range of physiologic processes. The group XIV subfamily of CTLDs are comprised of CD93, CD248/endosialin, CLEC14a, and thrombomodulin/CD141, and have important roles in creating and maintaining blood vessels, organizing extracellular matrix, and balancing pro- and anti-coagulative processes. As such, dysregulation in the expression and downstream signaling pathways of these proteins often lead to clinically relevant pathology.
View Article and Find Full Text PDFBackground: Targeting of solid cancers with chimeric antigen receptor (CAR)-T cells is limited by the lack of suitable tumor-specific antigens and the immunosuppressive, desmoplastic tumor microenvironment that impedes CAR-T cell infiltration, activity and persistence. We hypothesized that targeting the endosialin (CD248) receptor, strongly expressed by tumor-associated pericytes and perivascular cancer-associated fibroblasts, would circumvent these challenges and offer an exciting antigen for CAR-T cell therapy due to the close proximity of target cells to the tumor vasculature, the limited endosialin expression in normal tissues and the lack of phenotype observed in endosialin knockout mice.
Methods: We generated endosialin-directed E3K CAR-T cells from three immunocompetent mouse strains, BALB/c, FVB/N and C57BL/6.
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