The metastatic T‐cell hybridoma antigen/P‐selectin glycoprotein ligand 1 is required for hematogenous metastasis of lymphomas

Using variants of the murine BW5147 lymphoma cell‐line, we have previously identified 3 monoclonal antibodies (MAbs) that discriminate between metastatic and nonmetastatic BW5147‐derived T‐cell hybridomas and lymphomas, as well as BW5147‐unrelated T‐lymphomas. These MAbs were reported to recognize an identical membrane‐associated sialoglycoprotein, termed “metastatic T‐cell hybridoma antigen” (MTH‐Ag). Here, we document that the expression pattern of the MTH‐Ag on metastatic and nonmetastatic BW5147 variants correlates with that of the P‐selectin glycoprotein ligand 1 (PSGL‐1), a sialomucin involved in leukocyte recruitment to sites of inflammation. Moreover, the MAbs against the MTH‐Ag recognize PSGL‐1 when it is transfected in MTH‐Ag‐negative BW5147 variants, suggesting that the MTH‐Ag is PSGL‐1. Overexpression of MTH‐Ag/PSGL‐1 in MTH‐Ag‐negative BW5147 variants did not affect their in vivo malignancy. Yet, down‐regulation of MTH‐Ag/PSGL‐1 expression on metastatic, MTH‐Ag‐positive BW5147 variants, using an RNA interference (RNAi) approach, resulted, in a dose‐dependent manner, in a significant reduction of liver and spleen colonization and a delay in mortality of the recipient mice upon intravenous inoculation. Collectively, these results demonstrate that, although MTH‐Ag/PSGL‐1 overexpression alone may not be sufficient for successful dissemination and organ colonization, MTH‐Ag/PSGL‐1 plays a critical role in hematogenous metastasis of lymphoid cancer cells. © 2007 Wiley‐Liss, Inc.