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Tumor Engraftment in a Xenograft Mouse Model of Human Mantle Cell Lymphoma
Published on: March 30, 2018
Targeted disruption of the beta1 integrin gene in a lymphoma cell line greatly reduces metastatic capacity
P J Stroeken1, E A van Rijthoven, M A van der Valk
1Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam.
Abstract:
Integrins have been implicated in tumor metastasis. To investigate this, we generated beta1 integrin-negative double knockout (DKO) mutants of the highly metastatic ESb murine T-lymphoma cell line. The in vivo growth capacity of the mutants, which had lost alpha4beta1 and alpha6beta1 expression, was not altered, but their metastatic capacity was greatly reduced. Tail vein injection of 10(4) ESb and single-knockout cells led to death of all animals within 9-11 days. In contrast, only one-half of the animals injected with 10(4) DKO cells died, but much later, after 20-60 days. The other one-half remained disease-free for up to 100 days. Whereas ESb and single-knockout cells disseminated predominantly to liver and spleen, metastasis of DKO cells to these organs was rare, even after this prolonged period. Instead, skeletal muscles were invaded extensively. Metastatic capacity was largely restored in a DKO clone, which had been transfected with beta1 cDNA and expressed beta1 at similar levels as ESb cells. We conclude that beta1 integrins are essential for efficient liver and spleen colonization by the ESb lymphoma.
Insights
Beta1 integrins are crucial for the spread of ESb lymphoma cells to the liver and spleen. Removing these integrins significantly reduced metastasis, highlighting their role in tumor colonization.
Area of Science:
- Oncology
- Cell Biology
- Immunology
Background:
- Integrins play a role in tumor metastasis.
- Beta1 integrins are key cell surface receptors involved in cell adhesion and migration.
Purpose of the Study:
- To investigate the role of beta1 integrins in the metastatic capacity of the ESb murine T-lymphoma cell line.
- To determine the specific organs targeted by ESb lymphoma cells with altered beta1 integrin expression.
Main Methods:
- Generation of beta1 integrin-negative double knockout (DKO) mutants of the ESb cell line.
- Assessment of in vivo growth and metastatic capacity following tail vein injection.
- Analysis of organ colonization patterns using DKO and wild-type cells.
Main Results:
- DKO mutants showed significantly reduced metastatic capacity compared to wild-type ESb cells.
- Metastasis to liver and spleen was rare in DKO cell recipients.
- Skeletal muscle invasion was observed extensively in DKO cell recipients.
- Restoration of beta1 integrin expression in DKO cells recovered metastatic potential.
Conclusions:
- Beta1 integrins are essential for efficient liver and spleen colonization by the ESb lymphoma.
- The specific integrin subtypes alpha4beta1 and alpha6beta1 are implicated in this process.
- Targeting beta1 integrins may represent a therapeutic strategy to inhibit lymphoma metastasis.
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