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Hyaluronan‐independent lodgment of CD44 + lymphoma cells in lymphoid organs
Author(s) -
Vogt Sionov and Ronit,
Naor David
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970502)71:3<462::aid-ijc26>3.0.co;2-g
Subject(s) - cd44 , lymph node , lymph , biology , spleen , hyaluronic acid , lymphoma , lymphatic system , monoclonal antibody , lymph node stromal cell , cell culture , cancer research , microbiology and biotechnology , pathology , cell , immunology , antibody , medicine , anatomy , biochemistry , genetics
We previously found that monoclonal antibodies (MAbs) directed against the constant region of the CD44 molecule block lymph node infiltration of a mouse LB T‐cell lymphoma, suggesting a role for this glycoprotein in the LB cell dissemination process. In the present study, we investigated whether LB cells in the local tumor must undergo a change in the CD44 phenotype to be able to migrate to and invade the remote lymph nodes, and if hyaluronic acid (HA), the principal ligand of activated CD44, functions as a mediator in this process. We compared the in vivo behavior of a non‐HA‐binder LB cell line with that of a constitutive HA‐binder HA9 subline. Our results show that the lymphoid organ‐infiltrating LB cells express similar levels of pan‐CD44 and V4‐ and V6‐containing CD44 variants, as the corresponding cells in the local growth and the cultured LB cells. The tested CD44 phenotype of HA9 cells also remained unchanged during the metastatic process. Even after lymph node infiltration, LB cells remained incapable of binding HA, whereas the HA9 cells retained an efficient HA‐binding capacity. The constitutive HA‐binder HA9 cells that expressed an approximately 10‐fold higher level of pan‐CD44 than did the parental LB cells, as well as an elevated level of the V4 and V6 exon products formed a local tumor and invaded both lymph nodes and spleen, as did the parental LB cells, albeit at a much slower rate. Our finding indicates that there is no direct correlation between the amount of CD44 expressed on the cell surface, the HA‐binding capacity and tumorigenicity. Moreover, interaction with HA is not obligatory for LB cell localization in the lymphoid organs, and a tight cell‐HA interaction, as observed in HA9 cells, does not prevent tumor cell dissemination, although it may retard tumor spread. Int. J. Cancer 71:462‐469, 1997. © 1997 Wiley‐Liss Inc.