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.
Raes
Geert
G
Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium. geert.raes@vub.ac.be
Ghassabeh
Gholamreza Hassanzadeh
GH
Brys
Lea
L
Mpofu
Nonsikelelo
N
Verschueren
Hendrik
H
Vanhecke
Dominique
D
De Baetselier
Patrick
P
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D019040:E-Selectin / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D019337:Hematologic Neoplasms / Q000378:metabolism*; D006825:Hybridomas / Q000276:immunology* / Q000473:pathology; D008113:Liver Neoplasms / Q000517:prevention & control / Q000556:secondary; D016399:Lymphoma, T-Cell / Q000378:metabolism* / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D019007:P-Selectin / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D013160:Splenic Neoplasms / Q000517:prevention & control / Q000556:secondary; D014162:Transfection
D000951:Antigens, Neoplasm; D019040:E-Selectin; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D034741:RNA, Small Interfering