Defining the role of bone marrow-derived cells in pre-metastatic niche formation

Monday, October 24, 2011 — Poster Session I
Noon – 2:00 p.m.	Natcher Conference Center	NCI	CANCER-10

Authors

• A Giles
• C Persenaire
• M Kasai
• R Kaplan

Abstract

The ability of tumor cells to metastasize to distant tissues is the most lethal aspect of cancer. Tumors elicit changes in the microenvironment at sites of future metastases prior to the arrival of metastatic cells. Vascular endothelial growth factor receptor 1 (VEGFR1) expressing bone marrow-derived cells (BMDCs) migrate to sites of metastases in response to tumor or tumor-conditioned medium. These cells form clusters and, together with other recruited BMDCs and changes in the local stromal environment, form the pre-metastatic niche. However, the identity and functional significance of these cells during niche development and their mechanistic role in metastatic progression have not been fully elucidated. Here, I utilize multiple metastatic models to examine VEGFR1 populations in circulation and at metastatic sites. Mouse models of B16 melanoma or embryonal rhabdomyosarcoma display elevated VEGFR1+ cells in circulation. Analysis by flow cytometry reveals VEGFR1+ cells within metastatic sites represent a heterogeneous population of hematopoietic and myeloid lineages. Detailed phenotypical analyses of these cells will yield significant insights into lineage and developmental pathways required for initiation and maturation of the pre-metastatic niche and its impact on metastasis. Furthermore, this will contribute to characterizing the functional cross-talk between BMDCs, stroma and tumor.

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