Dataset Information

ACKR3 expression on diffuse large B cell lymphoma is required for tumor spreading and tissue infiltration.

ABSTRACT: Diffuse large B cell lymphoma (DLBCL) is the most frequent lymphoma accounting for more than the 30% of the cases. Involvement of extranodal sites, such as bone marrow and central nervous system, is associated with poor prognosis. A contribution of the chemokine system in these processes is assumed as it is known as a critical regulator of the metastatic process in cancer. The atypical chemokine receptor 3 (ACKR3), which does not couple to G-proteins and does not mediate cell migration, acts as a scavenger for CXCL11 and CXCL12, interfering with the tumor homing CXCL12/CXCR4 axis. Here, functional expression of ACKR3 in DLBCL cells was necessary for colonization of the draining lymph node in an in vivo subcutaneous lymphoma model. Moreover, in a disseminated in vivo lymphoma model, ACKR3 expression was required for bone marrow and brain invasion and local tumor growth. The present data unveil ACKR3 as potential therapeutic target for the control of tumor dissemination in DLBCL.

SUBMITTER: Puddinu V

PROVIDER: S-EPMC5689594 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

ACKR3 expression on diffuse large B cell lymphoma is required for tumor spreading and tissue infiltration.

Puddinu Viola V Casella Sabrina S Radice Egle E Thelen Sylvia S Dirnhofer Stefan S Bertoni Francesco F Thelen Marcus M

Oncotarget 20170629 49

Diffuse large B cell lymphoma (DLBCL) is the most frequent lymphoma accounting for more than the 30% of the cases. Involvement of extranodal sites, such as bone marrow and central nervous system, is associated with poor prognosis. A contribution of the chemokine system in these processes is assumed as it is known as a critical regulator of the metastatic process in cancer. The atypical chemokine receptor 3 (ACKR3), which does not couple to G-proteins and does not mediate cell migration, acts as ...[more]

PMID: 29156704

Similar Datasets

Project description:Background: Due to the high heterogeneity of diffuse large B-cell lymphoma (DLBCL), traditional chemotherapy treatment ultimately failed in one-third of the patients. Big challenges existed in finding how to accurately predict prognosis and provide individualized treatment. Hypoxia, although being a key factor in the development and progression of DLBCL, plays its role in DLBCL prognosis, which has yet to be fully explored. Methods: Data used in the current study were sourced from the Gene Expression Omnibus (GEO) database. DLBCL patients were divided according to different hypoxia-related subtypes based on the expressions of hypoxia-related genes (HRGs) relevant to survival. Differentially expressed genes (DEGs) between subtypes were identified using the limma package. Using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses, the prognostic signature was established to calculate risk scores. The tumor microenvironment (TME) in low- and high-risk groups was evaluated by single-sample gene set enrichment analysis (ssGSEA) and ESTIMATE. The chemotherapeutic sensitivity in two groups was assessed by IC50 values. Results: DLBCL patients were clustered into two hypoxia-related subtype groups according to different gene survival and expressions associated with increasing oxygen delivery and reducing oxygen consumption, and these two subtype groups were compared. Based on the differential expression, a risk model was established using univariate cox and LASSO regression analyses, FNDC1, ANTXR1, RARRES2, S100A9, and MT1M. The performance of the risk signature in predicting the prognosis of DLBCL patients was validated in the internal and external datasets, as evidenced by receiver operating characteristic (ROC) curves. In addition, we observed significant differences in the tumor microenvironment and chemotherapeutic response between low- and high-risk groups. Conclusion: Our study developed novel hypoxia-related subtypes in DLBCL and identified five prognostic signatures for DLBCL patients. These findings may enrich our understanding of the role of hypoxia in DLBCL and help improve the treatment of DLBCL patients.

Dataset Information

ACKR3 expression on diffuse large B cell lymphoma is required for tumor spreading and tissue infiltration.

Publications

ACKR3 expression on diffuse large B cell lymphoma is required for tumor spreading and tissue infiltration.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets