Resistance of ICAM-1-deficient mice to metastasis overcome by increased aggressiveness of lymphoma cells

Citation
M. Lalancette et al., Resistance of ICAM-1-deficient mice to metastasis overcome by increased aggressiveness of lymphoma cells, BLOOD, 95(1), 2000, pp. 314-319
Citations number
29
Categorie Soggetti
Hematology,"Cardiovascular & Hematology Research
Journal title
BLOOD
ISSN journal
00064971 → ACNP
Volume
95
Issue
1
Year of publication
2000
Pages
314 - 319
Database
ISI
SICI code
0006-4971(20000101)95:1<314:ROIMTM>2.0.ZU;2-8
Abstract
Our recent finding that resistance to lymphoma cell metastasis in intercell ular adhesion molecule-1-(ICAM-1)-deficient mice was manifested after homin g suggested that the mechanism could involve the capacity of ICAM-1 to indu ce, via leukocyte function-associated antigen-1 (LFA-1) signaling, the expr ession of new genes necessary for migration and survival of lymphoma cells after homing. This hypothesis would imply that lymphoma cells. on repeated metastatic cycles, would acquire such a highly aggressive phenotype that th ey no longer require contact with ICAM-1 at later stages of metastasis. We addressed this question by generating highly aggressive lymphoma variants t o determine if increased tumorigenicity would allow lymphoma cells to grow into tumors in ICAM-1-deficient mice. We found that on repeated in vivo pas sages, a selective pressure favored the lymphoma cells that constitutively express high levels of matrix metalloproteainse-9 (MMP-9), a gene associate d with a poor clinical outcome in non-Hodgkins's lymphoma. We further found that although the parent lymphoma cells could not grow tumors in ICAM-1-de ficient mice, the aggressive lymphoma variants could. This indicates that, at late stages of the disease, tumor cells with a high metastatic efficienc y, encoded by the repertoire of selected genes, no longer require some of t he signals normally delivered by cell adhesion molecules. In light of these findings, the possibility of inhibiting dissemination of lymphoma cells at the late stage of the disease by acting against cell adhesion molecules mu st be reconsidered.