Dataset Information

Tumor-Derived Thymic Stromal Lymphopoietin Expands Bone Marrow B-cell Precursors in Circulation to Support Metastasis

ABSTRACT: Immature B cells in the bone marrow emigrate into the spleen during adult lymphopoiesis. Here, we report that emigration is shifted to earlier B-cell stages in mice with orthotopic breast cancer, spontaneous ovarian cancer, and possibly in human breast carcinoma. Using mouse and human bone marrow aspirates and mouse models challenged with highly metastatic 4T1 breast cancer cells, we demonstrated that this was the result of secretion of thymic stromal lymphopoietin (TSLP) by cancer cells. First, TSLP downregulated surface expression of bone marrow (BM) retention receptors CXCR4 and VLA4 in B-cell precursors, increasing their motility and, presumably, emigration. Then, TSLP supported peripheral survival and proliferation of BM B-cell precursors such as pre-B–like cells. 4T1 cancer cells used the increased pool of circulating pre-B–like cells to generate metastasis-supporting regulatory B cells. As such, the loss of TSLP expression in cancer cells alone or TSLPR deficiency in B cells blocked both accumulation of pre-B–like cells in circulation and cancer metastasis, implying that the pre-B cell–TSLP axis can be an attractive therapeutic target. Significance: Cancer cells induce premature emigration of B-cell precursors from the bone marrow to generate regulatory B cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE164955 | GEO | 2021/01/17

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:The paper describes a model of tumor invasion to bone marrow. Created by COPASI 4.26 (Build 213) This model is described in the article: Modeling invasion of metastasizing cancer cells to bone marrow utilizing ecological principles Kun-Wan Chen, Kenneth J Pienta Theoretical Biology and Medical Modelling 2011, 8:36 Abstract: Background: The invasion of a new species into an established ecosystem can be directly compared to the steps involved in cancer metastasis. Cancer must grow in a primary site, extravasate and survive in the circulation to then intravasate into target organ (invasive species survival in transport). Cancer cells often lay dormant at their metastatic site for a long period of time (lag period for invasive species) before proliferating (invasive spread). Proliferation in the new site has an impact on the target organ microenvironment (ecological impact) and eventually the human host (biosphere impact). Results: Tilman has described mathematical equations for the competition between invasive species in a structured habitat. These equations were adapted to study the invasion of cancer cells into the bone marrow microenvironment as a structured habitat. A large proportion of solid tumor metastases are bone metastases, known to usurp hematopoietic stem cells (HSC) homing pathways to establish footholds in the bone marrow. This required accounting for the fact that this is the natural home of hematopoietic stem cells and that they already occupy this structured space. The adapted Tilman model of invasion dynamics is especially valuable for modeling the lag period or dormancy of cancer cells. Conclusions: The Tilman equations for modeling the invasion of two species into a defined space have been modified to study the invasion of cancer cells into the bone marrow microenvironment. These modified equations allow a more flexible way to model the space competition between the two cell species. The ability to model initial density, metastatic seeding into the bone marrow and growth once the cells are present, and movement of cells out of the bone marrow niche and apoptosis of cells are all aspects of the adapted equations. These equations are currently being applied to clinical data sets for verification and further refinement of the models. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

Tumor-Derived Thymic Stromal Lymphopoietin Expands Bone Marrow B-cell Precursors in Circulation to Support Metastasis

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets