Differential gene expression in murine large cell B-cell lymphoma metastatic variants

Joshi, Shantaram S.; Mittal, Amit; Wang, Peng; Joshi, Avadhut D.; Vu, Eileen; Wang, Xioujun

doi:10.1016/j.intimp.2008.05.007

Cited by 2 publications

(3 citation statements)

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“…26,27 We have observed a greater than twofold increase in the mRNA levels of cathepsins L, D and B in TSC1 KO versus WT B cells (not shown), suggesting that in B cells, mTOR activity is connected to expression of several cathepsin genes. Indeed, increase in cathepsin expression levels was observed in various types of non-Hodgkin's B-cell lymphomas, such as diffuse large B-cell lymphoma and chromic lymphocytic leukaemia, 39,40 and is associated with poor prognosis. We therefore conducted activity assays to establish a positive connection between mTORC1 activity and cathepsin activity in B cells (Figs 5 and 6).…”

Section: Discussionmentioning

confidence: 99%

“…38 This infers the opposite from what we have found for B cells and although in that study the activity of cathepsins was not visualized directly, it suggests a B-cell-specific cross talk between cathepsin activity and mTOR. Indeed, increase in cathepsin expression levels was observed in various types of non-Hodgkin's B-cell lymphomas, such as diffuse large B-cell lymphoma and chromic lymphocytic leukaemia, 39,40 and is associated with poor prognosis. Whether this is in a correlation with mTOR activity has not been investigated.…”

Section: Discussionmentioning

confidence: 99%

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mTORC1 activation in B cells confers impairment of marginal zone microarchitecture by exaggerating cathepsin activity

et al. 2018

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Mammalian target of rapamycin complex 1 (mTORC1) is a key regulator of cell metabolism and lymphocyte proliferation. It is inhibited by the tuberous sclerosis complex (TSC), a heterodimer of TSC1 and TSC2. Deletion of either gene results in robust activation of mTORC1. Mature B cells reside in the spleen at two major anatomical locations, the marginal zone (MZ) and follicles. The MZ constitutes the first line of humoral response against blood-borne pathogens and undergoes atrophy in chronic inflammation. In previous work, we showed that mice deleted for TSC1 in their B cells (TSC1 ) have almost no MZ B cells, whereas follicular B cells are minimally affected. To explore potential underlying mechanisms for MZ B-cell loss, we have analysed the spleen MZ architecture of TSC1 mice and found it to be severely impaired. Examination of lymphotoxins (LTα and LTβ) and lymphotoxin receptor (LTβR) expression indicated that LTβR levels in spleen stroma were reduced by TSC1 deletion in the B cells. Furthermore, LTα transcripts in B cells were reduced. Because LTβR is sensitive to proteolysis, we analysed cathepsin activity in TSC1 . A higher cathepsin activity, particularly of cathepsin B, was observed, which was reduced by mTORC1 inhibition with rapamycin in vivo. Remarkably, in vivo administration of a pan-cathepsin inhibitor restored LTβR expression, LTα mRNA levels and the MZ architecture. Our data identify a novel connection, although not elucidated at the molecular level, between mTORC1 and cathepsin activity in a manner relevant to MZ dynamics.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mTORC1 activation in B cells confers impairment of marginal zone microarchitecture by exaggerating cathepsin activity

et al. 2018

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“…Lymphoma metastasis is a multistep process that involves a series of mediating mechanisms including gene regulation, vascular adhesion and matrix invasion. Joshi et al [19] have investigated genes differentially expressed between low and high metastatic lymphoma sublines and found the differential expression of several genes, including insulin-like growth factor-IA and cyclin-D1, confirming that these genes were involved in lymphoma cell metastasis. Adhesion molecules regulate lymphoma metastasis by mediating the adhesion of disseminated tumour cells.…”

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confidence: 94%

Overexpression of apoptosis‐associated speck‐like protein in P388D1 murine lymphoma cells affects metastatic properties

Zhang

Lin

et al. 2011

Hematological Oncology

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Apoptosis-associated speck-like protein (ASC) is a bipartite adaptor molecule that participates in inflammation and apoptosis. ASC silencing has been observed in a significant proportion of human cancers. Here, we examined the role of ASC overexpression in the metastasis of the P388D1 murine lymphoma cell line to the liver, lung, spleen and kidney. First, we determined that the P388D1 cells express ASC. Then, ASC overexpression in P388D1 was achieved by transfecting pEGFP-ASC-C2 into the P388D1 cells. Furthermore, after the ASC-overexpressing P388D1 cells were injected into DBA/2 mice through the vena caudalis, their metastasis to the lung and the liver was significantly reduced in the pEGFP-ASC-C2-transfected group. These data indicate that ASC overexpression affects the in vivo metastatic properties of P388D1 cells.

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Differential gene expression in murine large cell B-cell lymphoma metastatic variants

Cited by 2 publications

References 30 publications

mTORC1 activation in B cells confers impairment of marginal zone microarchitecture by exaggerating cathepsin activity

mTORC1 activation in B cells confers impairment of marginal zone microarchitecture by exaggerating cathepsin activity

Overexpression of apoptosis‐associated speck‐like protein in P388D1 murine lymphoma cells affects metastatic properties

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