Dataset Information

Annexin 2-CXCL12 interactions regulate metastatic cell targeting and growth in the bone marrow.

ABSTRACT: Annexin 2 (ANXA2) plays a critical role in hematopoietic stem cell (HSC) localization to the marrow niche. In part, ANXA2 supports HSCs by serving as an anchor for stromal-derived factor-1 (CXCL12/SDF-1). Recently, it was demonstrated that prostate cancer cells, like HSCs, use ANXA2 to establish metastases in marrow. The present study determined the capacity of ANXA2 expression by bone marrow stromal cells (BMSC) to facilitate tumor recruitment and growth through ANXA2-CXCL12 interactions. Significantly more CXCL12 was expressed by BMSC(Anxa2) (+/+) than by BMSC(Anxa2) (-/-) resulting in more prostate cancer cells migrating and binding to BMSC(Anxa2) (+/+) than BMSC(Anxa2) (-/-), and these activities were reduced when CXCL12 interactions were blocked. To further confirm that BMSC signaling through ANXA2-CXCL12 plays a critical role in tumor growth, immunocompromised SCID mice were subcutaneously implanted with human prostate cancer cells mixed with BMSC(Anxa2) (+/+) or BMSC(Anxa2) (-/-). Significantly larger tumors grew in the mice when the tumors were established with BMSC(Anxa2) (+/+) compared with the tumors established with BMSC(Anxa2) (-/-). In addition, fewer prostate cancer cells underwent apoptosis when cocultured with BMSC(Anxa2) (+/+) compared with BMSC(Anxa2) (-/-), and similar results were obtained in tumors grown in vivo. Finally, significantly more vascular structures were observed in the tumors established with the BMSC(Anxa2) (+/+) compared with the tumors established with BMSC(Anxa2) (-/-). Thus, ANXA2-CXCL12 interactions play a crucial role in the recruitment, growth, and survival of prostate cancer cells in the marrow.The tumor microenvironment interaction between ANXA2-CXCL12 is critical for metastatic phenotypes and may impact chemotherapeutic potential.

SUBMITTER: Jung Y

PROVIDER: S-EPMC4297714 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Annexin 2-CXCL12 interactions regulate metastatic cell targeting and growth in the bone marrow.

Jung Younghun Y Wang Jingcheng J Lee Eunsohl E McGee Samantha S Berry Janice E JE Yumoto Kenji K Dai Jinlu J Keller Evan T ET Shiozawa Yusuke Y Taichman Russell S RS

Molecular cancer research : MCR 20140819 1

<h4>Unlabelled</h4>Annexin 2 (ANXA2) plays a critical role in hematopoietic stem cell (HSC) localization to the marrow niche. In part, ANXA2 supports HSCs by serving as an anchor for stromal-derived factor-1 (CXCL12/SDF-1). Recently, it was demonstrated that prostate cancer cells, like HSCs, use ANXA2 to establish metastases in marrow. The present study determined the capacity of ANXA2 expression by bone marrow stromal cells (BMSC) to facilitate tumor recruitment and growth through ANXA2-CXCL12 ...[more]

PMID: 25139998

Similar Datasets

Project description:It is widely accepted that complex interactions between cancer cells and their surrounding microenvironment contribute to disease development, chemo-resistance and disease relapse. In light of this observed interdependency, novel therapeutic interventions that target specific cancer stroma cell lineages and their interactions are being sought. Here we studied a mouse model of human T-cell acute lymphoblastic leukaemia (T-ALL) and used intravital microscopy to monitor the progression of disease within the bone marrow at both the tissue-wide and single-cell level over time, from bone marrow seeding to development/selection of chemo-resistance. We observed highly dynamic cellular interactions and promiscuous distribution of leukaemia cells that migrated across the bone marrow, without showing any preferential association with bone marrow sub-compartments. Unexpectedly, this behaviour was maintained throughout disease development, from the earliest bone marrow seeding to response and resistance to chemotherapy. Our results reveal that T-ALL cells do not depend on specific bone marrow microenvironments for propagation of disease, nor for the selection of chemo-resistant clones, suggesting that a stochastic mechanism underlies these processes. Yet, although T-ALL infiltration and progression are independent of the stroma, accumulated disease burden leads to rapid, selective remodelling of the endosteal space, resulting in a complete loss of mature osteoblastic cells while perivascular cells are maintained. This outcome leads to a shift in the balance of endogenous bone marrow stroma, towards a composition associated with less efficient haematopoietic stem cell function. This novel, dynamic analysis of T-ALL interactions with the bone marrow microenvironment in vivo, supported by evidence from human T-ALL samples, highlights that future therapeutic interventions should target the migration and promiscuous interactions of cancer cells with the surrounding microenvironment, rather than specific bone marrow stroma, to combat the invasion by and survival of chemo-resistant T-ALL cells.

Dataset Information

Annexin 2-CXCL12 interactions regulate metastatic cell targeting and growth in the bone marrow.

Publications

Annexin 2-CXCL12 interactions regulate metastatic cell targeting and growth in the bone marrow.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets