title: Cancer Cell Dissemination and Homing to the Bone Marrow in a Zebrafish Model.
abstract: Advancement of many solid tumors and hematologic malignancies is frequently characterized by dissemination and homing of cancer cells to the bone marrow (BM). Methods to quantitatively characterize these key steps of the metastatic cascade in mammalian models are currently limited and do not offer opportunities to perform rapid, large-scale genomic, or drug screening. Because of their optical clarity, we used zebrafish to develop an in vivo model of cancer cell dissemination and homing to the BM. We performed intracardiac injection of multiple myeloma (MM) cells derived from human BM or cell lines and monitored their migration to the caudal hematopoietic tissue (CHT), the region where hematopoiesis occurs in the zebrafish embryo, which recapitulates a BM-like niche. Transcriptomic analyses confirmed that MM cells homing to the CHT displayed gene-expression differences compared with MM cells outside of the CHT, including significant enrichment for genes known to regulate interleukin-6 (IL6) signaling, cell adhesion, and angiogenesis. Collectively, our findings point to the zebrafish as a valuable model in which to study cancer cell homing to the hematopoietic niche and to establish a screening platform for the identification of factors and mechanisms contributing to the early steps of bone metastasis.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Antonio
authors.initials: A
authors.lastname: Sacco
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Spedali Civili di Brescia, Centro per la Ricerca Onco-ematologica AIL, (CREA), Brescia, Italy.
authors.forename: Aldo M
authors.initials: AM
authors.lastname: Roccaro
authors.affiliation: Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jiantao
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mishima
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Michele
authors.initials: M
authors.lastname: Moschetta
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Spedali Civili di Brescia, Centro per la Ricerca Onco-ematologica AIL, (CREA), Brescia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Chiarini
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Munshi
authors.affiliation: Spedali Civili di Brescia, Centro per la Ricerca Onco-ematologica AIL, (CREA), Brescia, Italy. irene_ghobrial@dfci.harvard.edu rhandin@partners.org.
authors.forename: Robert I
authors.initials: RI
authors.lastname: Handin
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. irene_ghobrial@dfci.harvard.edu rhandin@partners.org.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Ghobrial
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D045744:Cell Line, Tumor; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D015027:Zebrafish