P-selectin glycoprotein ligand 1 promotes T cell lymphoma development and dissemination

• Published in: Translational oncology Vol. 14; no. 8; p. 101125
• Main Authors: Pereira, João L., Cavaco, Patrícia, da Silva, Ricardo C., Pacheco-Leyva, Ivette, Mereiter, Stefan, Pinto, Ricardo, Reis, Celso A., dos Santos, Nuno R.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.08.2021; Neoplasia Press; Elsevier
• Subjects: Dissemination; Lymphoma; Original; P-selectin glycoprotein ligand 1; T cell; Tumorigenesis; Tumorigenesis; Lymphoma; T cell; Dissemination; P-selectin glycoprotein ligand 1
• ISSN: 1936-5233; 1936-5233
• DOI: 10.1016/j.tranon.2021.101125

•PSGL-1 protein is frequently expressed at the surface of malignant T cells.•Enforced expression of PSGL-1 promotes T cell tumorigenesis in mice.•PSGL-1 expression accelerates malignant T cell dissemination from tumors to several organs.•PSGL-1 expression promotes malignant T cell expansion in kidneys and lungs. P-selectin glycoprotein ligand-1 (PSGL-1) is a membrane-bound glycoprotein expressed in lymphoid and myeloid cells. It is a ligand of P-, E- and L-selectin and is involved in T cell trafficking and homing to lymphoid tissues, among other functions. PSGL-1 expression has been implicated in different lymphoid malignancies, so here we aimed to evaluate the involvement of PSGL-1 in T cell lymphomagenesis and dissemination. PSGL-1 was highly expressed at the surface of human and mouse T cell leukemia and lymphoma cell lines. To assess its impact on T cell malignancies, we stably expressed human PSGL-1 (hPSGL-1) in a mouse thymic lymphoma cell line, which expresses low levels of endogenous PSGL-1 at the cell surface. hPSGL-1-expressing lymphoma cells developed subcutaneous tumors in athymic nude mice recipients faster than control empty vector or parental cells. Moreover, the kidneys, lungs and liver of tumor-bearing mice were infiltrated by hPSGL-1-expressing malignant T cells. To evaluate the role of PSGL-1 in lymphoma cell dissemination, we injected intravenously control and hPSGL-1-expressing lymphoma cells in athymic mice. Strikingly, PSGL-1 expression facilitated disease infiltration of the kidneys, as determined by histological analysis and anti-CD3 immunohistochemistry. Together, these results indicate that PSGL-1 expression promotes T cell lymphoma development and dissemination to different organs.