Development of a patient-derived xenograft (PDX) of breast cancer bone metastasis in a Zebrafish model

Laura Mercatali, Federico La Manna, Arwin Groenewoud, Roberto Casadei, Federica Recine, Giacomo Miserocchi, Federica Pieri, Chiara Liverani, Alberto Bongiovanni, Chiara Spadazzi, Alessandro de Vita, Gabri van der Pluijm, Andrea Giorgini, Roberto Biagini, Dino Amadori, Toni Ibrahim, Ewa Snaar-Jagalska

Research output: Contribution to journalArticle

Abstract

Bone metastasis is a complex process that needs to be better understood in order to help clinicians prevent and treat it. Xenografts using patient-derived material (PDX) rather than cancer cell lines are a novel approach that guarantees more clinically realistic results. A primary culture of bone metastasis derived from a 67-year-old patient with breast cancer was cultured and then injected into zebrafish (ZF) embryos to study its metastatic potential. In vivo behavior and results of gene expression analyses of the primary culture were compared with those of cancer cell lines with different metastatic potential (MCF7 and MDA-MB-231). The MCF7 cell line, which has the same hormonal receptor status as the bone metastasis primary culture, did not survive in the in vivo model. Conversely, MDA-MB-231 disseminated and colonized different parts of the ZF, including caudal hematopoietic tissues (CHT), revealing a migratory phenotype. Primary culture cells disseminated and in later stages extravasated from the vessels, engrafting into ZF tissues and reaching the CHT. Primary cell behavior reflected the clinical course of the patient’s medical history. Our results underline the potential for using PDX models in bone metastasis research and outline new methods for the clinical application of this in vivo model.

Original languageEnglish
Article number1375
JournalInternational Journal of Molecular Sciences
Volume17
Issue number8
DOIs
Publication statusPublished - Aug 22 2016

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Keywords

  • Bone metastasis
  • Breast cancer
  • Patient-derived xenograft
  • Zebrafish model

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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