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Protection from lymphoma cell metastasis in ICAM-1 mutant mice: a posthoming event
F Aoudjit1, E F Potworowski, T A Springer
1Immunology Research Center, Institut Armand-Frappier, Université du Québec, Canada.
Abstract:
It has been hypothesized that the intercellular adhesion receptors used by normal cells could also be operative in the spreading of circulating malignant cells to target organs. In the present work, we show that genetic ablation of the ICAM-1 gene confers resistance to T cell lymphoma metastasis. Following i.v. inoculation of LFA-1-expressing malignant T lymphoma cells, we found that ICAM-1-deficient mice were almost completely resistant to the development of lymphoid malignancy compared with wild-type control mice that developed lymphoid tumors in the kidneys, spleen, and liver. Histologic examinations confirmed that ICAM-1-deficient mice, in contrast to wild-type mice, had no evidence of lymphoid infiltration in these organs. The effect of ICAM-1 on T cell lymphoma metastasis was observed in two distinct strains of ICAM-1-deficient animals. Nonetheless, lymphoma cells migrated with the same efficiency to target organs in both normal and ICAM-1-deficient mice, indicating not only that ICAM-1 expression by the host is essential in lymphoma metastasis, but also that this is so at stages subsequent to homing and extravasation into target organs. These results point to posthoming events as a focus of future investigation on the control of metastasis mediated by ICAM-1.
Insights
Genetic ablation of intercellular adhesion molecule-1 (ICAM-1) confers resistance to T cell lymphoma metastasis. ICAM-1-deficient mice showed significantly reduced lymphoid malignancy, highlighting ICAM-1
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Intercellular adhesion receptors mediate normal cell interactions.
- These receptors may also play a role in malignant cell metastasis.
Purpose of the Study:
- To investigate the role of intercellular adhesion molecule-1 (ICAM-1) in T cell lymphoma metastasis.
- To determine if genetic absence of ICAM-1 impacts the development of lymphoid malignancy.
Main Methods:
- Genetic ablation of the ICAM-1 gene in mice.
- Intravenous inoculation of LFA-1-expressing malignant T lymphoma cells.
- Histologic examination of lymphoid infiltration in target organs (kidneys, spleen, liver).
Main Results:
- ICAM-1-deficient mice exhibited near-complete resistance to lymphoid malignancy compared to wild-type controls.
- No lymphoid infiltration was observed in target organs of ICAM-1-deficient mice.
- Lymphoma cell homing and extravasation were unaffected, suggesting ICAM-1 is crucial for post-homing metastasis.
Conclusions:
- Host ICAM-1 expression is essential for T cell lymphoma metastasis.
- ICAM-1's role in metastasis occurs after initial homing and extravasation.
- Future research should focus on ICAM-1-mediated post-homing events in metastasis control.